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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Turning an Aptamer into a Light-Switch Probe with
a Single Bioconjugation</title><author><name sortKey="Wickramaratne, Thakshila X0a M" sort="Wickramaratne, Thakshila X0a M" uniqKey="Wickramaratne T" first="Thakshila X0a M." last="Wickramaratne">Thakshila X0a M. Wickramaratne</name></author><author><name sortKey="Pierre, Valerie C" sort="Pierre, Valerie C" uniqKey="Pierre V" first="Valerie C." last="Pierre">Valerie C. Pierre</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25427946</idno><idno type="pmc">4306522</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306522</idno><idno type="RBID">PMC:4306522</idno><idno type="doi">10.1021/bc5003899</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000071</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000071</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Turning an Aptamer into a Light-Switch Probe with
a Single Bioconjugation</title><author><name sortKey="Wickramaratne, Thakshila X0a M" sort="Wickramaratne, Thakshila X0a M" uniqKey="Wickramaratne T" first="Thakshila X0a M." last="Wickramaratne">Thakshila X0a M. Wickramaratne</name></author><author><name sortKey="Pierre, Valerie C" sort="Pierre, Valerie C" uniqKey="Pierre V" first="Valerie C." last="Pierre">Valerie C. Pierre</name></author></analytic><series><title level="j">Bioconjugate Chemistry</title><idno type="ISSN">1043-1802</idno><idno type="eISSN">1520-4812</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="bc-2014-003899_0009" id="ab-tgr1"></graphic></p><p>We
describe a method for transforming a structure-switching aptamer
into a luminescent light-switch probe via a single conjugation. The
methodology is demonstrated using a known aptamer for Hg<sup>2+</sup> as a case study. This approach utilizes a lanthanide-based metallointercalator,
Eu-DOTA-Phen, whose luminescence is quenched almost entirely and selectively
by purines, but not at all by pyrimidines. This complex, therefore,
does not luminesce while intercalated in dsDNA, but it is bright red
when conjugated to a ssDNA that is terminated by several pyrimidines.
In its design, the light-switch probe incorporates a structure-switching
aptamer partially hybridized to its complementary strand. The lanthanide
complex is conjugated to either strand via a stable amide bond. Binding
of the analyte by the structure-switching aptamer releases the complementary
strand. This release precludes intercalation of the intercalator in
dsDNA, which switches on its luminescence. The resulting probe turns
on 21-fold upon binding to its analyte. Moreover, the structure switching
aptamer is highly selective, and the long luminescence lifetime of
the probe readily enables time-gating experiments for removal of the
background autofluorescence of the sample.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Liu, J W" uniqKey="Liu J">J. W. Liu</name></author><author><name sortKey="Cao, Z H" uniqKey="Cao Z">Z. H. Cao</name></author><author><name sortKey="Lu, Y" uniqKey="Lu Y">Y. Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stojanovic, M N" uniqKey="Stojanovic M">M. N. Stojanovic</name></author><author><name sortKey="De Prada, P" uniqKey="De Prada P">P. de Prada</name></author><author><name sortKey="Landry, D W" uniqKey="Landry D">D. W. Landry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stojanovic, M N" uniqKey="Stojanovic M">M. N. Stojanovic</name></author><author><name sortKey="De Prada, P" uniqKey="De Prada P">P. de Prada</name></author><author><name sortKey="Landry, D W" uniqKey="Landry D">D. W. Landry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hamaguchi, N" uniqKey="Hamaguchi N">N. Hamaguchi</name></author><author><name sortKey="Ellington, A" uniqKey="Ellington A">A. Ellington</name></author><author><name sortKey="Stanton, M" uniqKey="Stanton M">M. Stanton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Merino, E J" uniqKey="Merino E">E. J. Merino</name></author><author><name sortKey="Weeks, K M" uniqKey="Weeks K">K. M. Weeks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, T" uniqKey="Li T">T. Li</name></author><author><name sortKey="Dong, S J" uniqKey="Dong S">S. J. Dong</name></author><author><name sortKey="Wang, E" uniqKey="Wang E">E. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, H" uniqKey="Qin H">H. Qin</name></author><author><name sortKey="Ren, J" uniqKey="Ren J">J. Ren</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Luedtke, N W" uniqKey="Luedtke N">N. W. Luedtke</name></author><author><name sortKey="Wang, E" uniqKey="Wang E">E. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lv, L" uniqKey="Lv L">L. Lv</name></author><author><name sortKey="Guo, Z" uniqKey="Guo Z">Z. Guo</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Wang, E" uniqKey="Wang E">E. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, H Z" uniqKey="He H">H.-Z. He</name></author><author><name sortKey="Pui Yan, Ma V" uniqKey="Pui Yan M">Ma. V. Pui-Yan</name></author><author><name sortKey="Leung, K H" uniqKey="Leung K">K.-H. Leung</name></author><author><name sortKey="Shiu Hin Chan, D" uniqKey="Shiu Hin Chan D">D. Shiu-Hin Chan</name></author><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author><author><name sortKey="Cheng, Z" uniqKey="Cheng Z">Z. Cheng</name></author><author><name sortKey="Leung, C H" uniqKey="Leung C">C.-H. Leung</name></author><author><name sortKey="Ma, D L" uniqKey="Ma D">D.-L. Ma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author><author><name sortKey="Fang, X" uniqKey="Fang X">X. Fang</name></author><author><name sortKey="Bai, C" uniqKey="Bai C">C. Bai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author><author><name sortKey="Zhou, C" uniqKey="Zhou C">C. Zhou</name></author><author><name sortKey="Fang, X" uniqKey="Fang X">X. Fang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, C S" uniqKey="Zhou C">C. S. Zhou</name></author><author><name sortKey="Jiang, Y X" uniqKey="Jiang Y">Y. X. Jiang</name></author><author><name sortKey="Hou, S" uniqKey="Hou S">S. Hou</name></author><author><name sortKey="Ma, B C" uniqKey="Ma B">B. C. Ma</name></author><author><name sortKey="Fang, X H" uniqKey="Fang X">X. H. Fang</name></author><author><name sortKey="Li, M L" uniqKey="Li M">M. L. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Babu, E" uniqKey="Babu E">E. Babu</name></author><author><name sortKey="Singaravadivel, S" uniqKey="Singaravadivel S">S. Singaravadivel</name></author><author><name sortKey="Manojkumar, P" uniqKey="Manojkumar P">P. Manojkumar</name></author><author><name sortKey="Krishnasamy, S" uniqKey="Krishnasamy S">S. Krishnasamy</name></author><author><name sortKey="Kumar, G G" uniqKey="Kumar G">G. G. Kumar</name></author><author><name sortKey="Rajagopal, S" uniqKey="Rajagopal S">S. Rajagopal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, B" uniqKey="Li B">B. Li</name></author><author><name sortKey="Wei, H" uniqKey="Wei H">H. Wei</name></author><author><name sortKey="Dong, S" uniqKey="Dong S">S. Dong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, M S" uniqKey="Choi M">M. S. Choi</name></author><author><name sortKey="Yoon, M" uniqKey="Yoon M">M. Yoon</name></author><author><name sortKey="Baeg, J O" uniqKey="Baeg J">J. O. Baeg</name></author><author><name sortKey="Kim, J" uniqKey="Kim J">J. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pan, L" uniqKey="Pan L">L. Pan</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y. Huang</name></author><author><name sortKey="Wen, C C" uniqKey="Wen C">C. C. Wen</name></author><author><name sortKey="Zhao, S L" uniqKey="Zhao S">S. L. Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, Y" uniqKey="Luo Y">Y. Luo</name></author><author><name sortKey="Wu, P" uniqKey="Wu P">P. Wu</name></author><author><name sortKey="Hu, J" uniqKey="Hu J">J. Hu</name></author><author><name sortKey="He, S" uniqKey="He S">S. He</name></author><author><name sortKey="Hou, X" uniqKey="Hou X">X. Hou</name></author><author><name sortKey="Xu, K" uniqKey="Xu K">K. Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chiang, C X0a K" uniqKey="Chiang C">C.
K. Chiang</name></author><author><name sortKey="Huang, C C" uniqKey="Huang C">C. C. Huang</name></author><author><name sortKey="Liu, C W" uniqKey="Liu C">C. W. Liu</name></author><author><name sortKey="Chang, H T" uniqKey="Chang H">H. T. Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kong, L" uniqKey="Kong L">L. Kong</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J. Xu</name></author><author><name sortKey="Xu, Y Y" uniqKey="Xu Y">Y. Y. Xu</name></author><author><name sortKey="Xiang, Y" uniqKey="Xiang Y">Y. Xiang</name></author><author><name sortKey="Yuan, R" uniqKey="Yuan R">R. Yuan</name></author><author><name sortKey="Chai, Y Q" uniqKey="Chai Y">Y. Q. Chai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thibon, A" uniqKey="Thibon A">A. Thibon</name></author><author><name sortKey="Pierre, V C" uniqKey="Pierre V">V. C. Pierre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weitz, E A" uniqKey="Weitz E">E. A. Weitz</name></author><author><name sortKey="Chang, J Y" uniqKey="Chang J">J. Y. Chang</name></author><author><name sortKey="Rosenfield, A H" uniqKey="Rosenfield A">A. H. Rosenfield</name></author><author><name sortKey="Doan, P" uniqKey="Doan P">P. Doan</name></author><author><name sortKey="Pierre, V C" uniqKey="Pierre V">V. C. Pierre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Plush, S E" uniqKey="Plush S">S. E. Plush</name></author><author><name sortKey="Gunnlaugsson, T" uniqKey="Gunnlaugsson T">T. Gunnlaugsson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Law, G L" uniqKey="Law G">G.-L. Law</name></author><author><name sortKey="Pal, R" uniqKey="Pal R">R. Pal</name></author><author><name sortKey="Palsson, L O" uniqKey="Palsson L">L. O. Palsson</name></author><author><name sortKey="Parker, D" uniqKey="Parker D">D. Parker</name></author><author><name sortKey="Wong, K L" uniqKey="Wong K">K.-L. Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, D G" uniqKey="Smith D">D. G. Smith</name></author><author><name sortKey="Mcmahon, B K" uniqKey="Mcmahon B">B. K. McMahon</name></author><author><name sortKey="Pal, R" uniqKey="Pal R">R. Pal</name></author><author><name sortKey="Parker, D" uniqKey="Parker D">D. Parker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nutiu, R" uniqKey="Nutiu R">R. Nutiu</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nutiu, R" uniqKey="Nutiu R">R. Nutiu</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Friedman, A E" uniqKey="Friedman A">A. E. Friedman</name></author><author><name sortKey="Chambron, J C" uniqKey="Chambron J">J. C. Chambron</name></author><author><name sortKey="Sauvage, J P" uniqKey="Sauvage J">J. P. Sauvage</name></author><author><name sortKey="Turro, N J" uniqKey="Turro N">N. J. Turro</name></author><author><name sortKey="Barton, J K" uniqKey="Barton J">J. K. Barton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holmlin, R E" uniqKey="Holmlin R">R. E. Holmlin</name></author><author><name sortKey="Yao, J A" uniqKey="Yao J">J. A. Yao</name></author><author><name sortKey="Barton, J K" uniqKey="Barton J">J. K. Barton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, D S H" uniqKey="Chan D">D. S.-H. Chan</name></author><author><name sortKey="Lee, H M" uniqKey="Lee H">H.-M. Lee</name></author><author><name sortKey="Che, C M" uniqKey="Che C">C.-M. Che</name></author><author><name sortKey="Leung, C H" uniqKey="Leung C">C.-H. Leung</name></author><author><name sortKey="Ma, D L" uniqKey="Ma D">D.-L. Ma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, H K" uniqKey="Liu H">H.-K. Liu</name></author><author><name sortKey="Sadler, P J" uniqKey="Sadler P">P. J. Sadler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larsen, R W" uniqKey="Larsen R">R. W. Larsen</name></author><author><name sortKey="Jasuja, R" uniqKey="Jasuja R">R. Jasuja</name></author><author><name sortKey="Hetzler, R K" uniqKey="Hetzler R">R. K. Hetzler</name></author><author><name sortKey="Muraoka, P T" uniqKey="Muraoka P">P. T. Muraoka</name></author><author><name sortKey="Andrada, V G" uniqKey="Andrada V">V. G. Andrada</name></author><author><name sortKey="Jameson, D M" uniqKey="Jameson D">D. M. Jameson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smolensky, E D" uniqKey="Smolensky E">E. D. Smolensky</name></author><author><name sortKey="Peterson, K L" uniqKey="Peterson K">K. L. Peterson</name></author><author><name sortKey="Weitz, E A" uniqKey="Weitz E">E. A. Weitz</name></author><author><name sortKey="Lewandowski, C" uniqKey="Lewandowski C">C. Lewandowski</name></author><author><name sortKey="Pierre, V C" uniqKey="Pierre V">V. C. Pierre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weitz, E A" uniqKey="Weitz E">E. A. Weitz</name></author><author><name sortKey="Chang, J Y" uniqKey="Chang J">J. Y. Chang</name></author><author><name sortKey="Rosenfield, A H" uniqKey="Rosenfield A">A. H. Rosenfield</name></author><author><name sortKey="Pierre, V C" uniqKey="Pierre V">V. C. Pierre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bobba, G" uniqKey="Bobba G">G. Bobba</name></author><author><name sortKey="Bretonniere, Y" uniqKey="Bretonniere Y">Y. Bretonniere</name></author><author><name sortKey="Frias, J C" uniqKey="Frias J">J. C. Frias</name></author><author><name sortKey="Parker, D" uniqKey="Parker D">D. Parker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bobba, G" uniqKey="Bobba G">G. Bobba</name></author><author><name sortKey="Dickins, R S" uniqKey="Dickins R">R. S. Dickins</name></author><author><name sortKey="Kean, S D" uniqKey="Kean S">S. D. Kean</name></author><author><name sortKey="Mathieu, C E" uniqKey="Mathieu C">C. E. Mathieu</name></author><author><name sortKey="Parker, D" uniqKey="Parker D">D. Parker</name></author><author><name sortKey="Peacock, R D" uniqKey="Peacock R">R. D. Peacock</name></author><author><name sortKey="Siligardi, G" uniqKey="Siligardi G">G. Siligardi</name></author><author><name sortKey="Smith, M J" uniqKey="Smith M">M. J. Smith</name></author><author><name sortKey="Gareth X0a Williams, J A" uniqKey="Gareth X0a Williams J">J. A. Gareth
Williams</name></author><author><name sortKey="Geraldes, C F G C" uniqKey="Geraldes C">C. F. G. C. Geraldes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bobba, G" uniqKey="Bobba G">G. Bobba</name></author><author><name sortKey="Frias, J C" uniqKey="Frias J">J. C. Frias</name></author><author><name sortKey="Parker, D" uniqKey="Parker D">D. Parker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bobba, G" uniqKey="Bobba G">G. Bobba</name></author><author><name sortKey="Kean, S D" uniqKey="Kean S">S. D. Kean</name></author><author><name sortKey="Parker, D" uniqKey="Parker D">D. Parker</name></author><author><name sortKey="Beeby, A" uniqKey="Beeby A">A. Beeby</name></author><author><name sortKey="Baker, G" uniqKey="Baker G">G. Baker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cacheris, W P" uniqKey="Cacheris W">W. P. Cacheris</name></author><author><name sortKey="Quay, S C" uniqKey="Quay S">S. C. Quay</name></author><author><name sortKey="Rocklage, S M" uniqKey="Rocklage S">S. M. Rocklage</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hermann, P" uniqKey="Hermann P">P. Hermann</name></author><author><name sortKey="Kotek, J" uniqKey="Kotek J">J. Kotek</name></author><author><name sortKey="Kubicek, V" uniqKey="Kubicek V">V. Kubicek</name></author><author><name sortKey="Lukes, I" uniqKey="Lukes I">I. Lukes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z. Wang</name></author><author><name sortKey="Heon Lee, J" uniqKey="Heon Lee J">J. Heon Lee</name></author><author><name sortKey="Lu, Y" uniqKey="Lu Y">Y. Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kovacs, Z" uniqKey="Kovacs Z">Z. Kovacs</name></author><author><name sortKey="Sherry, A D" uniqKey="Sherry A">A. D. Sherry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moreau, J" uniqKey="Moreau J">J. Moreau</name></author><author><name sortKey="Guillon, E" uniqKey="Guillon E">E. Guillon</name></author><author><name sortKey="Pierrard, J C" uniqKey="Pierrard J">J. C. Pierrard</name></author><author><name sortKey="Rimbault, J" uniqKey="Rimbault J">J. Rimbault</name></author><author><name sortKey="Port, M" uniqKey="Port M">M. Port</name></author><author><name sortKey="Aplincourt, M" uniqKey="Aplincourt M">M. Aplincourt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Magda, D" uniqKey="Magda D">D. Magda</name></author><author><name sortKey="Wright, M" uniqKey="Wright M">M. Wright</name></author><author><name sortKey="Crofts, S" uniqKey="Crofts S">S. Crofts</name></author><author><name sortKey="Lin, A" uniqKey="Lin A">A. Lin</name></author><author><name sortKey="Sessler, J L" uniqKey="Sessler J">J. L. Sessler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holmlin, R E" uniqKey="Holmlin R">R. E. Holmlin</name></author><author><name sortKey="Dandliker, P J" uniqKey="Dandliker P">P. J. Dandliker</name></author><author><name sortKey="Barton, J K" uniqKey="Barton J">J. K. Barton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gaballah, S X0a T" uniqKey="Gaballah S">S.
T. Gaballah</name></author><author><name sortKey="Kerr, C E" uniqKey="Kerr C">C. E. Kerr</name></author><author><name sortKey="Eaton, B E" uniqKey="Eaton B">B. E. Eaton</name></author><author><name sortKey="Netzel, T L" uniqKey="Netzel T">T. L. Netzel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hara, K" uniqKey="Hara K">K. Hara</name></author><author><name sortKey="Kitamura, M" uniqKey="Kitamura M">M. Kitamura</name></author><author><name sortKey="Inoue, H" uniqKey="Inoue H">H. Inoue</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ihara, T" uniqKey="Ihara T">T. Ihara</name></author><author><name sortKey="Kitamura, Y" uniqKey="Kitamura Y">Y. Kitamura</name></author><author><name sortKey="Okada, K" uniqKey="Okada K">K. Okada</name></author><author><name sortKey="Tazaki, M" uniqKey="Tazaki M">M. Tazaki</name></author><author><name sortKey="Jyo, A" uniqKey="Jyo A">A. Jyo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graf, N" uniqKey="Graf N">N. Graf</name></author><author><name sortKey="Goritz, M" uniqKey="Goritz M">M. Goritz</name></author><author><name sortKey="Kramer, R" uniqKey="Kramer R">R. Kramer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kitamura, Y" uniqKey="Kitamura Y">Y. Kitamura</name></author><author><name sortKey="Ihara, T" uniqKey="Ihara T">T. Ihara</name></author><author><name sortKey="Tsujimura, Y" uniqKey="Tsujimura Y">Y. Tsujimura</name></author><author><name sortKey="Osawa, Y" uniqKey="Osawa Y">Y. Osawa</name></author><author><name sortKey="Jyo, A" uniqKey="Jyo A">A. Jyo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dubey, I Y" uniqKey="Dubey I">I. Y. Dubey</name></author><author><name sortKey="Dubey, L V" uniqKey="Dubey L">L. V. Dubey</name></author><author><name sortKey="Piletska, E V" uniqKey="Piletska E">E. V. Piletska</name></author><author><name sortKey="Piletsky, S A" uniqKey="Piletsky S">S. A. Piletsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andersen, C S" uniqKey="Andersen C">C. S. Andersen</name></author><author><name sortKey="Yan, H" uniqKey="Yan H">H. Yan</name></author><author><name sortKey="Gothelf, K V" uniqKey="Gothelf K">K. V. Gothelf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ghosh, S" uniqKey="Ghosh S">S. Ghosh</name></author><author><name sortKey="Pignot Paintrand, I" uniqKey="Pignot Paintrand I">I. Pignot-Paintrand</name></author><author><name sortKey="Dumy, P" uniqKey="Dumy P">P. Dumy</name></author><author><name sortKey="Defrancq, E" uniqKey="Defrancq E">E. Defrancq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ihara, T" uniqKey="Ihara T">T. Ihara</name></author><author><name sortKey="Kitamura, Y" uniqKey="Kitamura Y">Y. Kitamura</name></author><author><name sortKey="Tsujimura, Y" uniqKey="Tsujimura Y">Y. Tsujimura</name></author><author><name sortKey="Jyo, A" uniqKey="Jyo A">A. Jyo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hurtado, R R" uniqKey="Hurtado R">R. R. Hurtado</name></author><author><name sortKey="Harney, A S" uniqKey="Harney A">A. S. Harney</name></author><author><name sortKey="Heffern, M C" uniqKey="Heffern M">M. C. Heffern</name></author><author><name sortKey="Holbrook, R J" uniqKey="Holbrook R">R. J. Holbrook</name></author><author><name sortKey="Holmgren, R A" uniqKey="Holmgren R">R. A. Holmgren</name></author><author><name sortKey="Meade, T J" uniqKey="Meade T">T. J. Meade</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Bioconjug Chem</journal-id><journal-id journal-id-type="iso-abbrev">Bioconjug. Chem</journal-id><journal-id journal-id-type="publisher-id">bc</journal-id><journal-id journal-id-type="coden">bcches</journal-id><journal-title-group><journal-title>Bioconjugate Chemistry</journal-title></journal-title-group><issn pub-type="ppub">1043-1802</issn><issn pub-type="epub">1520-4812</issn><publisher><publisher-name>American Chemical
Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25427946</article-id><article-id pub-id-type="pmc">4306522</article-id><article-id pub-id-type="doi">10.1021/bc5003899</article-id><article-categories><subj-group><subject>Article</subject></subj-group></article-categories><title-group><article-title>Turning an Aptamer into a Light-Switch Probe with
a Single Bioconjugation</article-title></title-group><contrib-group><contrib contrib-type="author" id="ath1"><name><surname>Wickramaratne</surname><given-names>Thakshila
M.</given-names></name></contrib><contrib contrib-type="author" corresp="yes" id="ath2"><name><surname>Pierre</surname><given-names>Valerie C.</given-names></name><xref rid="cor1" ref-type="other">*</xref></contrib><aff id="aff1">Department of Chemistry,<institution>University of Minnesota</institution>, Minneapolis, Minnesota 55455,<country>United States</country></aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>Tel: <phone>(+1) 612 625 0921</phone>. E-mail: <email>pierre@umn.edu</email>.</corresp></author-notes><pub-date pub-type="pmc-release"><day>26</day><month>11</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>26</day><month>11</month><year>2014</year></pub-date><pub-date pub-type="ppub"><day>21</day><month>01</month><year>2015</year></pub-date><volume>26</volume><issue>1</issue><fpage>63</fpage><lpage>70</lpage><history><date date-type="received"><day>21</day><month>08</month><year>2014</year></date><date date-type="rev-recd"><day>05</day><month>11</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 American Chemical Society</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>American Chemical Society</copyright-holder><license><license-p>This is an open access article published under an ACS AuthorChoice <ext-link ext-link-type="uri" xlink:href="http://pubs.acs.org/page/policy/authorchoice_termsofuse.html">License</ext-link>, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.</license-p></license></permissions><abstract><p content-type="toc-graphic"><graphic xlink:href="bc-2014-003899_0009" id="ab-tgr1"></graphic></p><p>We
describe a method for transforming a structure-switching aptamer
into a luminescent light-switch probe via a single conjugation. The
methodology is demonstrated using a known aptamer for Hg<sup>2+</sup> as a case study. This approach utilizes a lanthanide-based metallointercalator,
Eu-DOTA-Phen, whose luminescence is quenched almost entirely and selectively
by purines, but not at all by pyrimidines. This complex, therefore,
does not luminesce while intercalated in dsDNA, but it is bright red
when conjugated to a ssDNA that is terminated by several pyrimidines.
In its design, the light-switch probe incorporates a structure-switching
aptamer partially hybridized to its complementary strand. The lanthanide
complex is conjugated to either strand via a stable amide bond. Binding
of the analyte by the structure-switching aptamer releases the complementary
strand. This release precludes intercalation of the intercalator in
dsDNA, which switches on its luminescence. The resulting probe turns
on 21-fold upon binding to its analyte. Moreover, the structure switching
aptamer is highly selective, and the long luminescence lifetime of
the probe readily enables time-gating experiments for removal of the
background autofluorescence of the sample.</p></abstract><funding-group><funding-statement><funding-source>National Institutes of Health, United States</funding-source></funding-statement></funding-group><custom-meta-group><custom-meta><meta-name>document-id-old-9</meta-name><meta-value>bc5003899</meta-value></custom-meta><custom-meta><meta-name>document-id-new-14</meta-name><meta-value>bc-2014-003899</meta-value></custom-meta><custom-meta><meta-name>ccc-price</meta-name><meta-value></meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec sec-type="intro" id="sec1"><title>Introduction</title><p>Aptamers, single-stranded
oligonucleotides that bind with high
affinity and high selectivity to a selected target such as a protein,
a small molecule, or a metal ion, are increasingly used in therapeutics,
diagnosis, and detection.<sup><xref ref-type="bibr" rid="ref1">1</xref></sup> Luminescent
analogs have been prevalent for the latter two applications due to
the widespread use of the technique. Indeed, significant work has
already been published on the design of fluorescent aptamer-based
probes, most commonly and successfully with approaches involving molecular
beacons<sup><xref ref-type="bibr" rid="ref2">2</xref>−<xref ref-type="bibr" rid="ref5">5</xref></sup> and aptamer-based G-quadruplex systems.<sup><xref ref-type="bibr" rid="ref6">6</xref>−<xref ref-type="bibr" rid="ref9">9</xref></sup> Unfortunately, this technology
requires multiple, often difficult, bioconjugation steps and it remains
ill-adapted to multiplex detection and applications in complex aqueous
or biological media. The first limitation with regard to synthesis
can, in theory, be met with the use of light-switch DNA intercalators,
molecules whose quantum yields vary greatly upon intercalation between
base pairs. However, intercalators have so far only been used in “label-free”
approaches, which consist of simply mixing the intercalators with
the aptamer. In each case, most of the dyes are intercalated both
in the absence and in the presence of the analyte. Consequently, the
responses observed were small and also turn-off.<sup><xref ref-type="bibr" rid="ref10">10</xref>−<xref ref-type="bibr" rid="ref19">19</xref></sup> The other two limitations, multiplex detection and detection in
a complex aqueous sample, could in theory be resolved with a lanthanide-based
probe.<sup><xref ref-type="bibr" rid="ref20">20</xref></sup> The narrow emission bands and
long luminescence lifetimes of lanthanide complexes make them uniquely
suited for multiplex detection and quantitative analysis in complex
media via time-gated measurements. Herein we report such a light-switch
lanthanide-based aptamer probe, with substantial turn-<italic>on</italic> and a long luminescence lifetime in the millisecond range. Its synthesis,
unlike that of most aptamer-based probes,<sup><xref ref-type="bibr" rid="ref2">2</xref>−<xref ref-type="bibr" rid="ref5">5</xref></sup> requires only one bioconjugation.
In comparison, other systems need an individual conjugation for both
the fluorophore and the quencher. The application of this methodology
can readily be expanded to other substrates and for multiplex detection.
The key to multiplex detection is simply to ensure that each aptamer
probe for each analyte has a unique reporter strand sequence and makes
use of a distinct lanthanide ion such as terbium, europium, thulium,
dysprosium, or samarium. Since the emission spectra of lanthanide
ions mostly do not overlap, they can be readily used for multiplex
detection. Multiplex detection with lanthanide ions has been extensively
reported by our group and others.<sup><xref ref-type="bibr" rid="ref21">21</xref>−<xref ref-type="bibr" rid="ref24">24</xref></sup></p><p>In terms of design, we
postulated that the first of the aforementioned
three limitations, the number of bioconjugation steps, could be resolved
via a single conjugation of a light-switch DNA intercalator to a structure-switching
aptamer. Structure-switching aptamers change their structure upon
binding to their cognate target, most often via the release of a shorter
complementary strand.<sup><xref ref-type="bibr" rid="ref25">25</xref>,<xref ref-type="bibr" rid="ref26">26</xref></sup> Judicious conjugation of an intercalating
dye to either strand of such an aptamer/complement duplex ensures
that the dye is completely intercalated only in the absence of the
analyte, but is not intercalated in the presence of the analyte (Figure <xref rid="fig1" ref-type="fig">1</xref>). If the intercalating dye itself is a light-switch,
then the aptamer probe will also be one. The probe is thus devised
to have a higher response than label-free intercalator-based systems,<sup><xref ref-type="bibr" rid="ref13">13</xref></sup> while at the same time limiting bioconjugation
to a single DNA strand. In this design, use of a dye that only luminesces
while intercalated will result in a turn-<italic>off</italic> probe,
while one that is quenched by stacking with base pairs will result
in a turn-<italic>on</italic> probe. Standard intercalators, which
are luminescent only when intercalated, would thus turn-<italic>off</italic>: in the absence of the analyte they would intercalate and be luminescent;
whereas in the presence of the analyte they would not intercalate
and not luminesce. Since turn-<italic>on</italic> probes are generally
preferred for practical applications, this design excludes the use
of common light-switch intercalators such as dppz-based ruthenium<sup><xref ref-type="bibr" rid="ref27">27</xref></sup> or osmium complexes,<sup><xref ref-type="bibr" rid="ref28">28</xref></sup> platinum complexes,<sup><xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref></sup> or organo-intercalators such
as ethidium bromide.<sup><xref ref-type="bibr" rid="ref31">31</xref></sup> Instead, we postulated
that the desired response could be achieved with lanthanide complexes
whose luminescence is nearly completely quenched upon intercalation
in double-stranded DNA (dsDNA). Our complex works as a turn-<italic>on</italic> probe because its response to intercalation is reversed:
it is not luminescent when intercalated (i.e., in the absence of the
analyte) but is luminescent when not intercalated (i.e., in the presence
of the analyte). A further advantage of using lanthanides is that
they also solve the other two limitations mentioned above of current
molecular beacons. The long luminescence lifetimes of lanthanide complexes,
typically in the millisecond range for Eu<sup>III</sup> and Tb<sup>III</sup>, enable facile time-gating experiments whereby the background
autofluorescence of the sample is removed. Lanthanides have multiple
emission bands which are also narrow. These narrow emission bands
with limited overlap further enable simultaneous detection of multiple
analytes in the same sample. If bands which do not overlap at all
are chosen, multiple probes with different lanthanides can be used
simultaneously in the same medium to test several analytes.</p><fig id="fig1" position="float"><label>Figure 1</label><caption><p>Proposed mode
of action of aptamer light-switch, Eu-AptaSwitch
(<bold>1</bold>). In the absence of Hg<sup>2+</sup>, the Eu<sup>III</sup> complex intercalates in dsDNA. Photoelectron transfer from the purines
to the phenanthridine antenna quenches the luminescence of Eu<sup>III</sup>. Binding of Hg<sup>2+</sup> by the aptamer releases the
short complementary strand, thereby preventing intercalation of the
Eu<sup>III</sup> complex and turning on its luminescence.</p></caption><graphic xlink:href="bc-2014-003899_0001" id="gr1" position="float"></graphic></fig><p>This design thus requires a lanthanide complex
not only capable
of intercalating in dsDNA, but whose luminescence is substantially
affected by the oligonucleotide. Our group<sup><xref ref-type="bibr" rid="ref21">21</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref33">33</xref></sup> and Parker’s<sup><xref ref-type="bibr" rid="ref34">34</xref>−<xref ref-type="bibr" rid="ref37">37</xref></sup> have previously demonstrated
that the luminescence of phenanthridine-based terbium and europium
complexes can be nearly completely quenched upon intercalation in
dsDNA. This effect, which is likely the result of photoelectron transfer
from stacked purines to the excited state of the chromophore, was
the basis behind the recent design of our probe for GTP and ATP detection.<sup><xref ref-type="bibr" rid="ref21">21</xref>,<xref ref-type="bibr" rid="ref33">33</xref></sup> Importantly, although both purines efficiently quench the lanthanide-centered
emission of this complex, neither of the two pyrimidines does. Our
probe, Eu-AptaSwitch (<bold>1</bold>), was thus constructed by conjugating
the phenanthridine-based lanthanide complex to the DNA strand of the
structure-switching aptamer that is mostly composed of thymidines
and cytidines (Figure <xref rid="fig2" ref-type="fig">2</xref>). The shorter complementary
strand is thus primarily composed of adenosines and guanosines. The
probe was designed to function as follows (Figure <xref rid="fig1" ref-type="fig">1</xref>). In the absence of the analyte, i.e., when the phenanthridine
is intercalated in the dsDNA, the probe is in the <italic>off</italic> mode. Photoelectron transfer (PeT) from the stacked purine bases
quenches the lanthanide luminescence. Binding of the analyte by the
aptamer releases the short complementary strand. At this point, intercalation
and quenching of the phenanthridine by purines are no longer possible.
Therefore, the luminescence of the lanthanide complex turns <italic>on</italic>.</p><fig id="fig2" position="float"><label>Figure 2</label><caption><p>Chemical structure of Eu-AptaSwitch (<bold>1</bold>).
The Eu<sup>III</sup> complex is conjugated to the aptamer via a C9
alkyl chain.
The two oligonucleotides are annealed prior to use.</p></caption><graphic xlink:href="bc-2014-003899_0002" id="gr2" position="float"></graphic></fig><p>A note on the stability of the metal complex used
for detection
and diagnosis. The probe Eu-AptaSwitch (<bold>1</bold>) incorporates
a macrocyclic polyaminocarboxylate ligand which renders the complex
both thermodynamically stable and kinetically inert. Lanthanide complexes
used for biological and medical applications must be stable and inert
so as to minimize the risk of trans-metalation with Ca<sup>2+</sup> and trans-ligation of the lanthanide with endogenous ligands such
as phosphates.<sup><xref ref-type="bibr" rid="ref38">38</xref></sup> Although more difficult
to synthesize than their linear analogs, macrocyclic DOTA-type chelates,
such as the one used in this study, are more appropriate for detection
of analytes in biological or environmental aqueous systems due to
their kinetic inertness. Furthermore, the overall positively charged
lanthanide complexes of DOTA tetraamide (DOTAm) ligands are kinetically
more inert than DOTA analogues as a result of the decreased basicity
of the nitrogen atoms.<sup><xref ref-type="bibr" rid="ref39">39</xref></sup></p><p>As a proof
of principle, we applied our concept to a structure-switching
aptamer previously reported for Hg<sup>2+</sup>.<sup><xref ref-type="bibr" rid="ref40">40</xref></sup> This aptamer makes use of the ability of thymidines to
coordinate Hg<sup>2+</sup> in a T-Hg<sup>2+</sup>-T fashion. Therefore,
the lanthanide complex was conjugated to the thymidine-rich strand
that binds Hg<sup>2+</sup> as opposed to its shorter complementary
strand. Note that in order to further increase the turn-<italic>on</italic> response of the probe, some of the purine bases in the mercury-binding
strand reported by Lu<sup><xref ref-type="bibr" rid="ref40">40</xref></sup> were replaced by
pyrimidines (third and fifth positions, A to C and G to C, respectively).
We anticipate that this design can be applied to any structure-switching
aptamer, regardless of how the aptamer binds its analyte.</p></sec><sec id="sec2"><title>Results and Discussion</title><p>The molecular probe Eu-AptaSwitch (<bold>1</bold>) was synthesized
according to Scheme <xref rid="sch1" ref-type="scheme">1</xref> from three advanced intermediates:
DO2A<sup><italic>t</italic></sup>Bu (<bold>2</bold>),<sup><xref ref-type="bibr" rid="ref41">41</xref></sup> the phenanthridine acetamide arm (<bold>3</bold>),<sup><xref ref-type="bibr" rid="ref33">33</xref></sup> and the bridging arm (<bold>5</bold>). The syntheses
of the former two were previously reported in the literature. Coupling
of the phenanthridine arm (<bold>3</bold>) to DO2A<sup><italic>t</italic></sup>Bu (<bold>2</bold>) followed by that of the bridging arm (<bold>5</bold>). yielded the fully protected ligand (<bold>6</bold>). Treatment
under acidic conditions deprotected the acids and the amine simultaneously,
thereby yielding the free ligand which was metalated with Eu<sup>III</sup> under slightly basic aqueous conditions. Note that as for any DOTA-type
complex, long reaction times are needed to ensure full complexation
of the lanthanide by the macrocycle.<sup><xref ref-type="bibr" rid="ref42">42</xref></sup> Advantageously,
the stability of the resulting amine-terminated complex enables subsequent
conjugation to any molecule containing a carboxylate. For our intended
application, the complex was reacted with the DADE-terminated aptamer
oligonucleotide while on solid support. DADE (decanoic acid diester)
is a commercially available preactivated carboxyl linker that enables
facile conjugation to the Eu<sup>III</sup>-complex all the while being
long enough for the phenanthridine to intercalate in the dsDNA (Figure <xref rid="fig2" ref-type="fig">2</xref>). Cleavage of the bioconjugate from its solid support,
followed by deprotection of the bases and purification by reverse
phase high pressure liquid chromatography (RP-HPLC), yielded the Eu<sup>III</sup> ssDNA conjugate (<bold>9</bold>) that was annealed with
the short complementary strand to yield the luminescent probe Eu-AptaSwitch
(<bold>1</bold>). Notably, bioconjugation was only possible with a
lanthanide complex containing an amine and a DNA terminated with an
activated carboxylic acid. Our multiple attempts at reversing the
functional groups, that is, to conjugate a Eu complex with a pendant
acid or activated acid to an amine-terminated oligonucleotide, were
all unsuccessful, regardless of the coupling agent used. This also
highlights the difficulty of conjugating metal complexes to DNA.<sup><xref ref-type="bibr" rid="ref2">2</xref>−<xref ref-type="bibr" rid="ref4">4</xref>,<xref ref-type="bibr" rid="ref43">43</xref>−<xref ref-type="bibr" rid="ref54">54</xref></sup> The synthesis described above should be applicable to the conjugation
of other types of metal complexes to DNA for therapeutic and diagnostic
purposes.</p><fig id="sch1" position="float"><label>Scheme 1</label><caption><title>Synthesis of Eu-AptaSwitch (1)</title><p id="s1fn1">Experimental
conditions: (a)
Et<sub>3</sub>N, CHCl<sub>3</sub>, 62 °C, 18 h; (b) Cs<sub>2</sub>CO<sub>3</sub>, CH<sub>3</sub>CN, 82 °C, 18 h; (c) HCl, CH<sub>3</sub>OH, rt, 5 d; (d) EuCl<sub>3</sub>·6H<sub>2</sub>O, LiOH,
H<sub>2</sub>O, pH 8, 70 °C, 76 h; (e) conjugation of the aptamer
to the DADE linker (on solid support) in phosphate buffer, pH 8, 15
h; deprotection: 30% NH<sub>3</sub>, 65 °C, 5 h; (f) complementary
strand, PBS, 95 °C for 15 min, slow cooling.</p></caption><graphic xlink:href="bc-2014-003899_0008" id="gr3" position="float"></graphic></fig><p>The time-gated emission profile of the probe in the absence and
presence of its analyte is shown in Figure <xref rid="fig3" ref-type="fig">3</xref>. As expected, annealing the Eu-ssDNA (<bold>9</bold>) conjugate
with the complementary strand quenches most of the metal-centered
luminescence; the luminescence of the annealed Eu-AptaSwitch (<bold>1</bold>) is only 4% that of the ssDNA conjugate (<bold>9</bold>).
This result is consistent with intercalation of the phenanthridine
in the dsDNA; resulting photoelectron transfer from the purine bases
to the antenna quenches the lanthanide-based emission. Importantly,
the luminescence of Eu<sup>III</sup> is fully recovered upon addition
of Hg<sup>2+</sup>. This observation is in agreement with binding
of Hg<sup>2+</sup> by its structure-switching aptamer concomitant
with release of the complementary strand such that the phenanthridine
can no longer intercalate in dsDNA. Since PeT from purine bases to
the antenna is no longer possible, luminescence of Eu<sup>III</sup> is recovered. This design enables not only a complete recovery of
the lanthanide emission, but also a substantial 21-fold turn-<italic>on</italic> which is comparable to that of other light-switch probes.
Support for our proposed mechanism of action comes from three observations.
First, the luminescence of the unconjugated Eu complex (<bold>8</bold>) is identical to that of the Eu-ssDNA conjugate (<bold>9</bold>);
they both have the same excitation and emission profiles and the same
quantum yield. Second, the luminescence of the probe after addition
of Hg<sup>2+</sup> is also identical to that of the Eu-ssDNA conjugate
(<bold>9</bold>, same excitation and emission profiles, and same quantum
yield). Last, heating the probe past its melting point in the absence
of Hg<sup>2+</sup>, which also liberates the Eu-complex by unfolding
the DNA, also turns the Eu luminescence back on. The combination of
these three observations strongly supports our proposed mechanism.</p><fig id="fig3" position="float"><label>Figure 3</label><caption><p>Time-gated
emission profiles of Eu-DNA conjugate (<bold>9</bold>) (solid line),
Eu-AptaSwitch (<bold>1</bold>) (dotted line), Eu-AptaSwitch·Hg<sup>2+</sup>(dashed line). Experimental conditions: [Eu-DNA conjugate]
= [Eu-AptaSwitch] = 20 μM, [Hg<sup>2+</sup>] = 250 μM,
PBS buffer, pH = 7.0, <italic>T</italic> = 20 °C, time-delay
= 0.1 ms, slit widths = 20 nm, excitation at 271 nm.</p></caption><graphic xlink:href="bc-2014-003899_0003" id="gr4" position="float"></graphic></fig><p>Notably, such a turn-<italic>on</italic> is readily
observable
with the naked eye upon illumination with a standard portable UV-lamp
(Figure <xref rid="fig4" ref-type="fig">4</xref>). The characteristic luminescence
of the probe is only apparent in the presence of 10 equiv of Hg<sup>2+</sup>. Although Eu emits in the red, the probe appears purple
to the naked eye. Indeed, pure Eu-centered emission can only be observed
with time-gating, as was performed in all of the titrations. Without
time-gating and with the naked eye, one sees a combination of the
Eu-centered emission (red) and the left-over emission from the phenanthridine
antenna which is not transferred to the lanthanide (blue). The combination
of the red Eu emission and the blue antenna emission give the overall
purple color seen in the photo taken with a standard hand-held camera.
This light-switch response thus bodes well for future application
of this technology to the detection of other analytes without the
need for a spectrophotometer. Moreover, the probe detects its analyte
rapidly; the luminescence turn-<italic>on</italic> is observed in
1 min after adding mercury at room temperature.</p><fig id="fig4" position="float"><label>Figure 4</label><caption><p>Luminescence of Eu-AptaSwitch
(<bold>1</bold>) upon excitation
with a portable UV lamp in the absence (a) and presence (b) of 10
equiv of Hg<sup>II</sup>. Experimental conditions: PBS, pH 7.0, rt,
λ<sub>excitation</sub> = 254 nm.</p></caption><graphic xlink:href="bc-2014-003899_0004" id="gr5" position="float"></graphic></fig><p>Time-gated luminescence titration of Eu-AptaSwitch (<bold>1</bold>) in the presence of Hg<sup>2+</sup> is shown in Figure <xref rid="fig5" ref-type="fig">5</xref>. Turn-<italic>on</italic> in the presence of low
concentration of mercury is shown in the inset. The very long lifetime
characteristic of Eu<sup>III</sup>-centered luminescence, a requirement
for time-gating experiments, is ideally suited for titrations in complex
aqueous media. Note that, as for Lu’s probe,<sup><xref ref-type="bibr" rid="ref40">40</xref></sup> the titration curve of Eu-AptaSwitch can be fitted with
a Hill coefficient of 2, suggesting a cooperative binding of Hg<sup>2+</sup> to the aptamer.</p><fig id="fig5" position="float"><label>Figure 5</label><caption><p>Time-gated luminescence of Eu-AptaSwitch (<bold>1</bold>) with
increasing concentration of Hg<sup>2+</sup>. Experimental conditions:
[Eu-AptaSwitch] = 20 μM, PBS buffer, pH = 7.0, <italic>T</italic> = 20 °C, time-delay = 0.1 ms, slit widths = 20 nm, excitation
at 271 nm, emission integrated from 450 to 750 nm, error bars represent
SD, <italic>n</italic> = 3. Inset: data points at low concentrations
of Hg<sup>2+</sup>.</p></caption><graphic xlink:href="bc-2014-003899_0005" id="gr6" position="float"></graphic></fig><p>Importantly, conjugating
the Eu complex to the aptamer does not
changes its affinity for Hg<sup>2+</sup>, nor its selectivity over
competing divalent metal. The selectivity of the probe toward the
alkali earth and transition metals Mg<sup>2+</sup>, Ca<sup>2+</sup>, Zn<sup>2+</sup>, Cd<sup>2+</sup>, Mn<sup>2+</sup>, Co<sup>2+</sup>, Pb<sup>2+</sup>, Ni<sup>2+</sup>, and Cu<sup>2+</sup> is shown
in Figure <xref rid="fig6" ref-type="fig">6</xref>. The probe does not turn on upon
addition of an excess of each competing metal ions. Importantly, the
presence of these metal ions also does not influence the response
of the probe toward Hg<sup>2+</sup>. The light-switch probe (<bold>1</bold>) remains highly selective, as was the original probe reported
by Lu and co-workers. The fact that the metallointercalator does not
influence the response of the aptamer bodes well for other applications.</p><fig id="fig6" position="float"><label>Figure 6</label><caption><p>Selectivity
of Eu-AptaSwitch (<bold>1</bold>). Gray bars represent
the luminescence response after adding 250 μM metal ion (except
Hg<sup>2+</sup>, which is only 25 μM). Black bars represent
the luminescence response after adding 25 μM of Hg<sup>2+</sup> to the probe containing 250 μM metal ion. Experimental conditions:
[Eu-AptaSwitch] = 20 μM, PBS buffer, pH = 7.0, <italic>T</italic> = 20 °C, time-delay = 0.1 ms, excitation at 271 nm, emission
at 592 nm, error bars represent SD, <italic>n</italic> = 3.</p></caption><graphic xlink:href="bc-2014-003899_0006" id="gr7" position="float"></graphic></fig><p>A distinct advantage of lanthanides
in the design of probes is
their very long luminescence lifetime, in the millisecond range, that
is uniquely suited for applications in complex aqueous media. With
such long lifetimes, the background autofluorescence of the sample
can readily be removed with time-gating experiments allowing for more
accurate measurements at low turn-<italic>on</italic>. Indeed, as
can be seen in Figure <xref rid="fig7" ref-type="fig">7</xref>, the Eu-AptaSwitch
probe is also efficient in Human serum. A lower turn-<italic>on</italic> is observed for a given concentration of Hg<sup>2+</sup> in serum
as compared to phosphate-buffered saline. This difference could be
due to partial quenching of the lanthanide emission by serum protein
and/or to binding of Hg<sup>2+</sup> by serum proteins, which decreases
the concentration of Hg<sup>2+</sup> available to the probe.</p><fig id="fig7" position="float"><label>Figure 7</label><caption><p>Time-gated
luminescence of Eu-AptaSwitch (<bold>1</bold>) in human
serum with increasing concentration of Hg<sup>2+</sup>. Experimental
conditions: [Eu-AptaSwitch] = 20 μM, <italic>T</italic> = 20
°C, time-delay = 0.1 ms, excitation at 271 nm, emission at 592
nm, error bars represent SD, <italic>n</italic> = 3.</p></caption><graphic xlink:href="bc-2014-003899_0007" id="gr8" position="float"></graphic></fig></sec><sec sec-type="conclusions" id="sec3"><title>Conclusion</title><p>In conclusion, a novel
approach to the design of luminescent aptamer
probes that makes use of a light-switch lanthanide intercalator is
reported. Compared to beacon-type approaches, this approach only requires
a single conjugation, and therefore enables a more facile synthesis.
As opposed to the label-free approaches that also employ DNA intercalators,
our approach yields not only a turn-<italic>on</italic> response but
also a substantially greater response. Moreover, the structure switching
aptamer ensures the selectivity of the probe, while the long luminescence
lifetime and the narrow emission bands of lanthanide metals are expected
to facilitate multiplex detection in a single, complex aqueous sample.</p></sec><sec id="sec4"><title>Experimental
Procedures</title><sec id="sec4.1"><title>General Considerations</title><p>Unless otherwise noted, starting
materials were obtained from commercial suppliers and used without
further purification. DNA was purchased from Trilink Biotechnologies.
Water was distilled and further purified by a Millipore cartridge
system (resistivity 1.8 × 10<sup>7</sup> Ω). Flash chromatography
was performed on Salicycle Silica Gel (230–400 mesh) or Brockmann
activated aluminum oxide (neutral, 60 mesh). <sup>1</sup>H NMR spectra
were recorded on a Varian 300 or Varian 500 at 300 or 500 MHz respectively,
and <sup>13</sup>C NMR spectra on a Varian 300 at 75 MHz at the LeClaire-Dow
Instrumentation Facility at the Department of Chemistry at the University
of Minnesota, Twin-Cities. The residual solvent peak was used as an
internal reference. Data for <sup>1</sup>H NMR are recorded as follows:
chemical shift (δ, ppm), multiplicity (s, singlet; br s, broad
singlet; d, doublet; t, triplet; q, quartet; m, multiplet), integration,
coupling constant (Hz). Data for <sup>13</sup>C NMR are reported in
terms of chemical shift (δ, ppm). Mass spectra (LR = low resolution;
HR = high resolution; ESI = electrospray ionization) were recorded
on a Bruker BioTOF II at the Waters Center of Innovation for Mass
Spectrometry at the Department of Chemistry at the University of Minnesota,
Twin-Cities. Liquid Chromatography–Mass Spectrometry, HPLC-ESI-MS
were performed on an Agilent 1100 capillary HPLC-ion trap mass spectrometer
(Agilent Technologies) at the Mass Spectrometry facility at the Masonic
Cancer Center at the University of Minnesota. A Zorbax 300SB-C8 column
(150 mm × 0.3 mm, 3.5 μm, Agilent Technologies) was eluted
at a flow rate of 9 μL/min with a gradient of 15 mM ammonium
acetate and 5–16% acetonitrile in over 14 min and then up to
90% over 2 min. The column was maintained at 40 °C. The mass
spectrometer was operated in the negative mode for the analyses of
oligonucleotide conjugates. UV–vis data was obtained on a Cary
Bio 100 UV–vis spectrophotometer. Fluorescence data was acquired
on a Varian Cary Eclipse Spectrophotometer using a quartz cell with
a path length of 10 mm, excitation slit width of 20 nm, and emission
slit width of 20 nm at 20 °C.</p></sec><sec id="sec4.2"><title>Di-<italic>tert</italic>-butyl 2,2′-(4-(2-oxo-2-((phenanthridin-6-ylmethyl)amino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate
(<bold>4</bold>)</title><p>Di-<italic>tert</italic>-butyl 2,2′-(1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate
(<bold>2</bold>) and 2-chloro-<italic>N</italic>-(phenanthridine-6-ylmethyl)acetamide
(<bold>3</bold>) were synthesized according to previously published
procedures.<sup><xref ref-type="bibr" rid="ref21">21</xref>,<xref ref-type="bibr" rid="ref41">41</xref></sup> A solution of 2-chloro-<italic>N</italic>-(phenanthridine-6-ylmethyl)acetamide (<bold>3</bold>)
(101 mg, 0.355 mmol) in CHCl<sub>3</sub> (10 mL) was added to
a solution of di-<italic>tert</italic>-butyl 2,2′-(1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate
(<bold>2</bold>) (285 mg, 0.711 mmol) and triethylamine (59 μL,
0.48 mmol) in CHCl<sub>3</sub> (10 mL) under N<sub>2</sub> (<italic>g</italic>). The reaction mixture was heated to reflux under N<sub>2</sub> (<italic>g</italic>) for 20 h then allowed to cool to room
temperature. The product was purified by chromatography over alumina
eluting with a gradient of CH<sub>2</sub>Cl<sub>2</sub> to 10% CH<sub>3</sub>OH/90% CH<sub>2</sub>Cl<sub>2</sub>. The product was obtained
as a yellow oil (200 mg, 87%). <sup>1</sup>H NMR (500 MHz, CDCl<sub>3</sub>) δ 8.65 (d, <italic>J</italic> = 8.5 Hz,1H), 8.57 (d, <italic>J</italic> = 8.0 Hz, 1H), 8.36 (d, <italic>J</italic> = 7.5 Hz, 1H),
8.16 (m, 1H), 7.88 (t, <italic>J</italic> = 7.5 Hz, 1H), 7.73 (m,
3H), 5.14 (s, 2H), 2.91 (m, 22H), 1.30 (s, 18H); <sup>13</sup>C NMR
(125 MHz, CDCl<sub>3</sub>) δ 171.8, 170.5, 143.4, 133.0, 131.2,
129.6, 129.0, 128.1, 127.3, 126.5, 125.6, 124.5, 124.3, 122.7, 122.4,
81.5, 58.0, 54.6, 52.5, 49.8, 47.9, 43.1, 28.1; HRMS (ESI) calc for
[C<sub>36</sub>H<sub>52</sub>DN<sub>6</sub>O<sub>5</sub>]<sup>+</sup> ([M+D]<sup>+</sup>): <italic>m</italic>/<italic>z</italic> 649.4056,
found: 649.4070.</p></sec><sec id="sec4.3"><title><italic>tert</italic>-Butyl (2-(2-bromoacetamido)ethyl)carbamate
(<bold>5</bold>)</title><p>A solution of K<sub>2</sub>CO<sub>3</sub> (202 mg, 1.46 mmol) in water (20 mL) and a solution of bromoacetyl
bromide (132 μL, 1.51 mmol) in CH<sub>2</sub>Cl<sub>2</sub> (20
mL) were simultaneously added over 30 min to a solution of <italic>tert</italic>-butyl (2-aminoethyl)carbamate (200 μL, 1.26 mmol)
in CH<sub>2</sub>Cl<sub>2</sub> (50 mL) cooled to 0 °C. The reaction
mixture was subsequently allowed to warm to room temperature and stirred
for an additional 1.5 h. The reaction mixture was rinsed with water
(2 × 50 mL) and saturated NaCl (<italic>aq</italic>) (1 × 50 mL),
dried over magnesium sulfate, and filtered. The solvents were removed
under reduced pressure to yield the product <bold>5</bold> as a white
solid (315 mg, 90%). <sup>1</sup>H NMR (300 MHz, CDCl<sub>3</sub>)
δ 5.21 (s, 2H), 3.61 (t, <italic>J</italic> = 6.6 Hz, 2H), 3.06
(m, 2H), 1.39 (s, 1H); <sup>13</sup>C NMR (60 MHz, CDCl<sub>3</sub>) δ 166.5, 156.5, 79.7, 53.2, 39.5, 41.2, 28.0; HRMS (ESI)
calc for C<sub>9</sub>H<sub>18</sub>NaN<sub>2</sub>O<sub>3</sub>Br
([M + Na]<sup>+</sup>): <italic>m</italic>/<italic>z</italic> 303.0315,
found: 303.0377.</p></sec><sec id="sec4.4"><title>Di-<italic>tert</italic>-butyl 2,2′-(4-(2-((2-((<italic>tert</italic>-butoxycarbonyl)amino)ethyl)amino)-2-oxoethyl)-10-(2-oxo-2-((phenanthridin-6-ylmethyl)amino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate
(<bold>6</bold>)</title><p>Di-<italic>tert</italic>-butyl 2,2′-(4-(2-oxo-2-((phenanthridin-6-ylmethyl)amino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate
(<bold>4</bold>, 50 mg, 0.077 mmol) and Cs<sub>2</sub>CO<sub>3</sub> (50 mg, 0.15 mmol) were added to a solution of <italic>tert</italic>-butyl (2-(2-bromoacetamido)ethyl)carbamate (<bold>5</bold>, 43 mg,
0.15 mmol) in acetonitrile (25 mL). The reaction mixture was heated
for 18 h at 82 °C. The reaction mixture was then allowed to cool
to room temperature and the solvents were removed under reduced pressure
yielding the protected ligand <bold>6</bold> as a yellow oil which
was used immediately in the next step. <sup>1</sup>H NMR (500 MHz,
CDCl<sub>3</sub>) δ 8.79 (d, <italic>J</italic> = 8.1 Hz, 1H),
8.71 (d, <italic>J</italic> = 7.8 Hz, 1H), 8.30 (d, <italic>J</italic> = 8.1 Hz, 1H), 8.09 (d, <italic>J</italic> = 7.8 Hz, 1H), 7.93
(t, <italic>J</italic> = 8.1 Hz, 1H), 7.75 (m, 3H), 4.34 (s, 2H),
3.25 (m, 4H), 2.71 (m, 24H), 1.43 (s, 18H), 1.36 (s, 9H); <sup>13</sup>C NMR (125 MHz, CDCl<sub>3</sub>) δ 176.2, 175.5, 174.5, 174.1,
172.0, 144.3, 134.5, 132.5, 130.4, 130.1, 129.1, 128.6, 126.9, 125.7,
125.6, 124.0, 123.6, 118.5, 82.1, 80.1, 80.0, 64.5, 62.6, 59.8, 59.4,
57.7, 57.2, 55.9, 55.4, 53.7, 44.6, 41.8, 41.1, 40.1, 28.9, 28.7,
28.5, 28.4, 28.3; HRMS (ESI) calc for [C<sub>45</sub>H<sub>68</sub>NaN<sub>8</sub>O<sub>8</sub>]<sup>+</sup> ([M + Na]<sup>+</sup>): <italic>m</italic>/<italic>z</italic> 871.5052, found: 871.5034.</p></sec><sec id="sec4.5"><title>2,2′-(4-(2-((2-Aminoethyl)amino)-2-oxoethyl)-10-(2-oxo-2-((phenanthridin-6-ylmethyl)amino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetic
acid (<bold>7</bold>)</title><p>Di-<italic>tert</italic>-butyl 2,2′-(4-(2-((2-((<italic>tert</italic>-butoxycarbonyl)amino)ethyl)amino)-2-oxoethyl)-10-(2-oxo-2-((phenanthridin-6-ylmethyl)amino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate
(<bold>6</bold>) (65 mg, 0.077 mmol) was dissolved in CH<sub>3</sub>OH (5 mL) and concentrated HCl (<italic>aq</italic>) (1 mL) was added.
The reaction was stirred for 5 days at room temperature after which
the volatiles were removed under reduced pressure. The resulting oil
was washed with cold CH<sub>3</sub>OH (8 × 5 mL). Yield (42 mg,
79% over two steps). <sup>1</sup>H NMR (500 MHz, CDCl<sub>3</sub>)
δ 8.52 (d, 2H), 8.17 (s, 1H), 7.81 (m, 5H), 4.42 (s, 2H), 2.40–3.80
(m, 28H); <sup>13</sup>C NMR (125 MHz, CDCl<sub>3</sub>) δ 176.2,
174.7, 158.3, 156.6, 141.6, 131.6, 130.8, 130.3, 129.2, 128.0, 127.4,
125.0, 124.4, 124.0, 123.7, 123.2,122.4, 63.5, 60.9, 56.7, 56.2, 52.3,
48.4, 45.5, 42.7, 39.5, 39.2, 38.0, 37.7, 36.6, 36.4; HRMS (ESI) calc
for [C<sub>32</sub>H<sub>41</sub>Na<sub>2</sub>LiN<sub>8</sub>O<sub>6</sub>]<sup>+</sup> ([M+2Na+Li]<sup>+</sup>): <italic>m</italic>/<italic>z</italic> 687.4049, found: 687.4069. See <xref rid="notes-2" ref-type="notes">Supporting Information Figure S1</xref> for <sup>1</sup>H NMR spectra
of the free ligand <bold>7</bold>.</p></sec><sec id="sec4.6"><title>Eu-DO2A-Phen-Amine (<bold>8</bold>)</title><p>2,2′-(4-(2-((2-Aminoethyl)amino)-2-oxoethyl)-10-(2-oxo-2-((phenanthridin-6-ylmethyl)amino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetic
acid (<bold>7</bold>) (42 mg, 66 μmol) was dissolved in milliQ
water (5 mL) and magnetically stirred. EuCl<sub>3</sub>·6H<sub>2</sub>O (25 mg, 66 μmol) was added to the reaction mixture
and the pH was adjusted to 8 with LiOH. The reaction mixture was stirred
for 76 h at 70 °C, filtered, and the solvents were removed under
reduced pressure. See <xref rid="notes-2" ref-type="notes">Supporting Information Figure
S2</xref> for the <sup>1</sup>H NMR spectra and <xref rid="notes-2" ref-type="notes">Supporting Information Figure S3</xref> for the HPLC trace of the
complex. HRMS (ESI) calc for [C<sub>33</sub>H<sub>46</sub>EuN<sub>8</sub>O<sub>6</sub>]<sup>+</sup> ([M + H]<sup>+</sup>): <italic>m</italic>/<italic>z</italic> 787.2798, found: 787.2731.</p></sec><sec id="sec4.7"><title>Eu-DNA Conjugate
(<bold>9</bold>)</title><p>Eu-DO2A-Phen-Amine
(<bold>8</bold>, 2 mg, 5 μmol) was dissolved in phosphate buffer
saline (80 μL) at pH 8. After stirring for 5 min, the amine
was added to the protected aptamer (50 nmol) on beads in DMF (20 μL).
The reaction mixture was mixed slowly for 15 h. The supernatant was
decanted and the beads were rinsed with mQ water (2 × 1 mL), CH<sub>3</sub>OH (2 ×
1 mL), and CH<sub>3</sub>CN (2 × 1 mL). The beads were dried
under reduced pressure for 15 min and 30% NH<sub>3</sub> (<italic>aq</italic>) (750 μL) was added. The mixture was then heated
at 65 °C for 5 h. The mixture was decanted and the beads
were rinsed with water. The combined supernatants were concentrated
under reduced pressure. The DNA conjugate was purified by high performance
liquid chromatography (HPLC) using a Zorbax 300SB-C8 9.4 × 250
mm, 5 μm Agilent Technologies) column. Solvents were eluted
at a flow rate of 2.5 mL/min with a gradient of 12–14% acetonitrile
in 15 mM ammonium acetate over 35 min and 90% over 2 min. Conjugates
were desalted by passing through NAP-5 columns and the eluent was
concentrated. Capillary HPLC-MS (ESI)<sup>−</sup> calc for
the Eu-DNA conjugate <bold>9</bold> ([M-H]<sup>−</sup>): <italic>m</italic>/<italic>z</italic> 10938.7; found: 10938.6. See <xref rid="notes-2" ref-type="notes">Supporting Information Figure S4</xref> for the LC-MS
and ESI-MS of the Eu-DNA conjugate probe <bold>9</bold>.</p></sec><sec id="sec4.8"><title>Eu-AptaSwitch
(<bold>1</bold>)</title><p>Eu-DNA conjugate (<bold>9</bold>) was heated
with a molar equivalent of the complementary
strand (100 μM) in PBS buffer (pH 7.0) at 95 °C for 15
min and allowed to cool to room temperature over 15 h.</p></sec></sec></body><back><notes id="notes-2" notes-type="si"><title>Supporting Information Available</title><p><sup>1</sup>H NMR spectrum
of the ligand DO2A-Phen-Amine (<bold>7</bold>) and the complex [EuDO2A-Phen-Amine]<sup>+</sup> (<bold>8</bold>), HPLC-ESI<sup>–</sup>-MS spectrum
of Eu-DNA Conjugate (<bold>9</bold>). This material is available free
of charge via the Internet at <uri xlink:href="http://pubs.acs.org">http://pubs.acs.org</uri>.</p></notes><sec sec-type="supplementary-material"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="sifile1"><media xlink:href="bc5003899_si_001.pdf"><caption><p>bc5003899_si_001.pdf</p></caption></media></supplementary-material></sec><notes id="notes-1" notes-type="conflict-of-interest"><p>The authors
declare no competing financial interest.</p></notes><ack><title>Acknowledgments</title><p>This work
was supported by the National Science Foundation
(CAREER 1151665) and by the NIH Clinical and Translational Science
Institute at the University of Minnesota (8UL1TR000114). The Masonic
Cancer Center Mass Spectrometry Facility, a University of Minnesota
shared resource was supported by NIH grant P30CA77598. We thank Brock
Matter (Masonic Cancer Center Mass Spectrometry Facility) for his
help with developing the liquid chromatography mass spectrometry methodology.</p></ack><glossary id="dl1"><def-list><title>Abbreviations</title><def-item><term>DNA</term><def><p>deoxyribonucleic acid</p></def></def-item><def-item><term>dsDNA</term><def><p>double-stranded DNA</p></def></def-item><def-item><term>ssDNA</term><def><p>single-stranded
DNA</p></def></def-item><def-item><term>GTP</term><def><p>guanosine
triphosphate</p></def></def-item><def-item><term>ATP</term><def><p>adenosine triphosphate</p></def></def-item><def-item><term>UTP</term><def><p>uridine triphosphate</p></def></def-item><def-item><term>CTP</term><def><p>cytosine triphosphate</p></def></def-item><def-item><term>PeT</term><def><p>photoelectron transfer</p></def></def-item><def-item><term>DOTA</term><def><p>1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
acid</p></def></def-item><def-item><term>SD</term><def><p>standard
deviation</p></def></def-item><def-item><term>NMR</term><def><p>nuclear
magnetic resonance</p></def></def-item><def-item><term>HRMS</term><def><p>high resolution mass spectrometry</p></def></def-item><def-item><term>ESI</term><def><p>electrospray ionization</p></def></def-item><def-item><term>HPLC</term><def><p>high pressure liquid chromatography</p></def></def-item><def-item><term>DMF</term><def><p>dimethylformamide</p></def></def-item><def-item><term>UV–vis</term><def><p>ultraviolet–visible
light</p></def></def-item><def-item><term>PBS</term><def><p>phosphate-buffered
saline</p></def></def-item></def-list></glossary><ref-list><title>References</title><ref id="ref1"><mixed-citation publication-type="journal" id="cit1"><name><surname>Liu</surname><given-names>J. W.</given-names></name>; <name><surname>Cao</surname><given-names>Z. H.</given-names></name>; <name><surname>Lu</surname><given-names>Y.</given-names></name> (<year>2009</year>) <article-title>Functional
nucleic acid sensors</article-title>. <source>Chem. Rev.</source><volume>109</volume>, <fpage>1948</fpage>–<lpage>1998</lpage>.<pub-id pub-id-type="pmid">19301873</pub-id></mixed-citation></ref><ref id="ref2"><mixed-citation publication-type="journal" id="cit2"><name><surname>Stojanovic</surname><given-names>M. N.</given-names></name>; <name><surname>de Prada</surname><given-names>P.</given-names></name>; <name><surname>Landry</surname><given-names>D. W.</given-names></name> (<year>2000</year>) <article-title>Fluorescent
sensors based on aptamer
self-assembly</article-title>. <source>J. Am. Chem. Soc.</source><volume>122</volume>, <fpage>11547</fpage>–<lpage>11548</lpage>.</mixed-citation></ref><ref id="ref3"><mixed-citation publication-type="journal" id="cit3"><name><surname>Stojanovic</surname><given-names>M. N.</given-names></name>; <name><surname>de Prada</surname><given-names>P.</given-names></name>; <name><surname>Landry</surname><given-names>D. W.</given-names></name> (<year>2001</year>) <article-title>Aptamer-based
folding fluorescent
sensor for cocaine</article-title>. <source>J. Am. Chem. Soc.</source><volume>123</volume>, <fpage>4928</fpage>–<lpage>4931</lpage>.<pub-id pub-id-type="pmid">11457319</pub-id></mixed-citation></ref><ref id="ref4"><mixed-citation publication-type="journal" id="cit4"><name><surname>Hamaguchi</surname><given-names>N.</given-names></name>; <name><surname>Ellington</surname><given-names>A.</given-names></name>; <name><surname>Stanton</surname><given-names>M.</given-names></name> (<year>2001</year>) <article-title>Aptamer beacons for the direct detection
of proteins</article-title>. <source>Anal. Biochem.</source><volume>294</volume>, <fpage>126</fpage>–<lpage>131</lpage>.<pub-id pub-id-type="pmid">11444807</pub-id></mixed-citation></ref><ref id="ref5"><mixed-citation publication-type="journal" id="cit5"><name><surname>Merino</surname><given-names>E. J.</given-names></name>; <name><surname>Weeks</surname><given-names>K. M.</given-names></name> (<year>2003</year>) <article-title>Fluorogenic resolution of ligand
binding by a nucleic
acid aptamer</article-title>. <source>J. Am. Chem. Soc.</source><volume>125</volume>, <fpage>12370</fpage>–<lpage>12371</lpage>.<pub-id pub-id-type="pmid">14531655</pub-id></mixed-citation></ref><ref id="ref6"><mixed-citation publication-type="journal" id="cit6"><name><surname>Li</surname><given-names>T.</given-names></name>; <name><surname>Dong</surname><given-names>S. J.</given-names></name>; <name><surname>Wang</surname><given-names>E.</given-names></name> (<year>2010</year>) <article-title>A lead(II)-driven
DNA molecular device
for turn-on fluorescence detection of lead(II) ion with high selectivity
and sensitivity</article-title>. <source>J. Am. Chem. Soc.</source><volume>132</volume>, <fpage>13156</fpage>–<lpage>13157</lpage>.<pub-id pub-id-type="pmid">20822179</pub-id></mixed-citation></ref><ref id="ref7"><mixed-citation publication-type="journal" id="cit7"><name><surname>Qin</surname><given-names>H.</given-names></name>; <name><surname>Ren</surname><given-names>J.</given-names></name>; <name><surname>Wang</surname><given-names>J.</given-names></name>; <name><surname>Luedtke</surname><given-names>N. W.</given-names></name>; <name><surname>Wang</surname><given-names>E.</given-names></name> (<year>2010</year>) <article-title>G-quadruplex-modulated
fluorescence detection of potassium in the presence of a 3500-fold
excess of sodium ions</article-title>. <source>Anal. Chem.</source><volume>82</volume>, <fpage>8356</fpage>–<lpage>8360</lpage>.<pub-id pub-id-type="pmid">20804164</pub-id></mixed-citation></ref><ref id="ref8"><mixed-citation publication-type="journal" id="cit8"><name><surname>Lv</surname><given-names>L.</given-names></name>; <name><surname>Guo</surname><given-names>Z.</given-names></name>; <name><surname>Wang</surname><given-names>J.</given-names></name>; <name><surname>Wang</surname><given-names>E.</given-names></name> (<year>2012</year>) <article-title>G-quadruplex as signal transducer
for biorecognition events</article-title>. <source>Curr. Pharm. Des.</source><volume>18</volume>, <fpage>2076</fpage>–<lpage>2095</lpage>.<pub-id pub-id-type="pmid">22380517</pub-id></mixed-citation></ref><ref id="ref9"><mixed-citation publication-type="journal" id="cit9"><name><surname>He</surname><given-names>H.-Z.</given-names></name>; <name><surname>Pui-Yan</surname><given-names>Ma. V.</given-names></name>; <name><surname>Leung</surname><given-names>K.-H.</given-names></name>; <name><surname>Shiu-Hin Chan</surname><given-names>D.</given-names></name>; <name><surname>Yang</surname><given-names>H.</given-names></name>; <name><surname>Cheng</surname><given-names>Z.</given-names></name>; <name><surname>Leung</surname><given-names>C.-H.</given-names></name>; <name><surname>Ma</surname><given-names>D.-L.</given-names></name> (<year>2012</year>) <article-title>A label-free
G-quadruplex-based switch-on fluorescence assay for the selective
detection of ATP</article-title>. <source>Analyst</source><volume>137</volume>, <fpage>1538</fpage>–<lpage>1540</lpage>.<pub-id pub-id-type="pmid">22343772</pub-id></mixed-citation></ref><ref id="ref10"><mixed-citation publication-type="journal" id="cit10"><name><surname>Jiang</surname><given-names>Y.</given-names></name>; <name><surname>Fang</surname><given-names>X.</given-names></name>; <name><surname>Bai</surname><given-names>C.</given-names></name> (<year>2004</year>) <article-title>Signaling aptamer/protein
binding
by a molecular light switch complex</article-title>. <source>Anal. Chem.</source><volume>76</volume>, <fpage>5230</fpage>–<lpage>5235</lpage>.<pub-id pub-id-type="pmid">15373466</pub-id></mixed-citation></ref><ref id="ref11"><mixed-citation publication-type="journal" id="cit11"><name><surname>Wang</surname><given-names>J.</given-names></name>; <name><surname>Jiang</surname><given-names>Y.</given-names></name>; <name><surname>Zhou</surname><given-names>C.</given-names></name>; <name><surname>Fang</surname><given-names>X.</given-names></name> (<year>2005</year>) <article-title>Aptamer-based ATP assay
using a luminescent light switching complex</article-title>. <source>Anal. Chem.</source><volume>77</volume>, <fpage>3542</fpage>–<lpage>3546</lpage>.<pub-id pub-id-type="pmid">15924387</pub-id></mixed-citation></ref><ref id="ref12"><mixed-citation publication-type="journal" id="cit12"><name><surname>Zhou</surname><given-names>C. S.</given-names></name>; <name><surname>Jiang</surname><given-names>Y. X.</given-names></name>; <name><surname>Hou</surname><given-names>S.</given-names></name>; <name><surname>Ma</surname><given-names>B. C.</given-names></name>; <name><surname>Fang</surname><given-names>X. H.</given-names></name>; <name><surname>Li</surname><given-names>M. L.</given-names></name> (<year>2006</year>) <article-title>Detection of oncoprotein
platelet-derived growth factor using a fluorescent
signaling complex of an aptamer and TOTO</article-title>. <source>Anal.
Bioanal. Chem.</source><volume>384</volume>, <fpage>1175</fpage>–<lpage>1180</lpage>.<pub-id pub-id-type="pmid">16447044</pub-id></mixed-citation></ref><ref id="ref13"><mixed-citation publication-type="journal" id="cit13"><name><surname>Babu</surname><given-names>E.</given-names></name>; <name><surname>Singaravadivel</surname><given-names>S.</given-names></name>; <name><surname>Manojkumar</surname><given-names>P.</given-names></name>; <name><surname>Krishnasamy</surname><given-names>S.</given-names></name>; <name><surname>Kumar</surname><given-names>G. G.</given-names></name>; <name><surname>Rajagopal</surname><given-names>S.</given-names></name> (<year>2013</year>) <article-title>Aptamer-based label-free detection
of PDGF using ruthenium(II) complex as luminescent probe</article-title>. <source>Anal. Bioanal. Chem.</source><volume>405</volume>, <fpage>6891</fpage>–<lpage>6895</lpage>.<pub-id pub-id-type="pmid">23881364</pub-id></mixed-citation></ref><ref id="ref14"><mixed-citation publication-type="journal" id="cit14"><name><surname>Li</surname><given-names>B.</given-names></name>; <name><surname>Wei</surname><given-names>H.</given-names></name>; <name><surname>Dong</surname><given-names>S.</given-names></name> (<year>2007</year>) <article-title>Sensitive detection of protein by an aptamer-based
label-free fluorescing molecular switch</article-title>. <source>Chem.
Commun.</source><fpage>73</fpage>–<lpage>75</lpage>.</mixed-citation></ref><ref id="ref15"><mixed-citation publication-type="journal" id="cit15"><name><surname>Choi</surname><given-names>M. S.</given-names></name>; <name><surname>Yoon</surname><given-names>M.</given-names></name>; <name><surname>Baeg</surname><given-names>J. O.</given-names></name>; <name><surname>Kim</surname><given-names>J.</given-names></name> (<year>2009</year>) <article-title>Label-free dual assay
of DNA sequences and potassium ions using an aptamer probe and a molecular
light switch complex</article-title>. <source>Chem. Commun.</source><fpage>7419</fpage>–<lpage>7421</lpage>.</mixed-citation></ref><ref id="ref16"><mixed-citation publication-type="journal" id="cit16"><name><surname>Pan</surname><given-names>L.</given-names></name>; <name><surname>Huang</surname><given-names>Y.</given-names></name>; <name><surname>Wen</surname><given-names>C. C.</given-names></name>; <name><surname>Zhao</surname><given-names>S. L.</given-names></name> (<year>2013</year>) <article-title>Label-free fluorescence
probe based on structure-switching aptamer for the detection of interferon
gamma</article-title>. <source>Analyst</source><volume>138</volume>, <fpage>6811</fpage>–<lpage>6816</lpage>.<pub-id pub-id-type="pmid">24058925</pub-id></mixed-citation></ref><ref id="ref17"><mixed-citation publication-type="journal" id="cit17"><name><surname>Luo</surname><given-names>Y.</given-names></name>; <name><surname>Wu</surname><given-names>P.</given-names></name>; <name><surname>Hu</surname><given-names>J.</given-names></name>; <name><surname>He</surname><given-names>S.</given-names></name>; <name><surname>Hou</surname><given-names>X.</given-names></name>; <name><surname>Xu</surname><given-names>K.</given-names></name> (<year>2012</year>) <article-title>An oligonucleotide-based
label-free fluorescent sensor: highly sensitive and selective detection
of Hg<sup>2+</sup> in aqueous samples</article-title>. <source>Anal.
Methods</source><volume>4</volume>, <fpage>1310</fpage>–<lpage>1314</lpage>.</mixed-citation></ref><ref id="ref18"><mixed-citation publication-type="journal" id="cit18"><name><surname>Chiang</surname><given-names>C.
K.</given-names></name>; <name><surname>Huang</surname><given-names>C. C.</given-names></name>; <name><surname>Liu</surname><given-names>C. W.</given-names></name>; <name><surname>Chang</surname><given-names>H. T.</given-names></name> (<year>2008</year>) <article-title>Oligonucleotide-based
fluorescence probe for sensitive and selective detection of mercury(II)
in aqueous solution</article-title>. <source>Anal. Chem.</source><volume>80</volume>, <fpage>3716</fpage>–<lpage>3721</lpage>.<pub-id pub-id-type="pmid">18363331</pub-id></mixed-citation></ref><ref id="ref19"><mixed-citation publication-type="journal" id="cit19"><name><surname>Kong</surname><given-names>L.</given-names></name>; <name><surname>Xu</surname><given-names>J.</given-names></name>; <name><surname>Xu</surname><given-names>Y. Y.</given-names></name>; <name><surname>Xiang</surname><given-names>Y.</given-names></name>; <name><surname>Yuan</surname><given-names>R.</given-names></name>; <name><surname>Chai</surname><given-names>Y. Q.</given-names></name> (<year>2013</year>) <article-title>A universal
and label-free aptasensor for fluorescent detection of ATP and thrombin
based on SYBR Green I dye</article-title>. <source>Biosens. Bioelectron.</source><volume>42</volume>, <fpage>193</fpage>–<lpage>197</lpage>.<pub-id pub-id-type="pmid">23202351</pub-id></mixed-citation></ref><ref id="ref20"><mixed-citation publication-type="journal" id="cit20"><name><surname>Thibon</surname><given-names>A.</given-names></name>; <name><surname>Pierre</surname><given-names>V. C.</given-names></name> (<year>2009</year>) <article-title>Principles of responsive
lanthanide-based luminescent
probes for cellular imaging</article-title>. <source>Anal. Bioanal.
Chem.</source><volume>394</volume>, <fpage>107</fpage>–<lpage>120</lpage>.<pub-id pub-id-type="pmid">19283368</pub-id></mixed-citation></ref><ref id="ref21"><mixed-citation publication-type="journal" id="cit21"><name><surname>Weitz</surname><given-names>E. A.</given-names></name>; <name><surname>Chang</surname><given-names>J. Y.</given-names></name>; <name><surname>Rosenfield</surname><given-names>A. H.</given-names></name>; <name><surname>Doan</surname><given-names>P.</given-names></name>; <name><surname>Pierre</surname><given-names>V. C.</given-names></name> (<year>2013</year>) <article-title>Molecular
recognition and the basis for selective time-gated luminescent detection
of ATP and GTP</article-title>. <source>Chem. Sci.</source><volume>4</volume>, <fpage>4052</fpage>–<lpage>4060</lpage>.</mixed-citation></ref><ref id="ref22"><mixed-citation publication-type="journal" id="cit22"><name><surname>Plush</surname><given-names>S. E.</given-names></name>; <name><surname>Gunnlaugsson</surname><given-names>T.</given-names></name> (<year>2008</year>) <article-title>Solution studies of trimetallic lanthanide
luminescent
anion sensors: towards ratiometric sensing using an internal reference
channel</article-title>. <source>Dalton Trans.</source><fpage>3801</fpage>–<lpage>3804</lpage>.<pub-id pub-id-type="pmid">18629401</pub-id></mixed-citation></ref><ref id="ref23"><mixed-citation publication-type="journal" id="cit23"><name><surname>Law</surname><given-names>G.-L.</given-names></name>; <name><surname>Pal</surname><given-names>R.</given-names></name>; <name><surname>Palsson</surname><given-names>L. O.</given-names></name>; <name><surname>Parker</surname><given-names>D.</given-names></name>; <name><surname>Wong</surname><given-names>K.-L.</given-names></name> (<year>2009</year>) <article-title>Responsive and reactive
terbium complexes with an azaxanthone sensitiser and one naphthyl
group: applications in ratiometric oxygen sensing <italic>in vitro</italic> and in regioselective cell killing</article-title>. <source>Chem.
Commun.</source><fpage>7321</fpage>–<lpage>7323</lpage>.</mixed-citation></ref><ref id="ref24"><mixed-citation publication-type="journal" id="cit24"><name><surname>Smith</surname><given-names>D. G.</given-names></name>; <name><surname>McMahon</surname><given-names>B. K.</given-names></name>; <name><surname>Pal</surname><given-names>R.</given-names></name>; <name><surname>Parker</surname><given-names>D.</given-names></name> (<year>2012</year>) <article-title>Live cell imaging of
lysosomal pH changes with pH responsive ratiometric lanthanide probes</article-title>. <source>Chem. Commun.</source><volume>48</volume>, <fpage>8520</fpage>–<lpage>8522</lpage>.</mixed-citation></ref><ref id="ref25"><mixed-citation publication-type="journal" id="cit25"><name><surname>Nutiu</surname><given-names>R.</given-names></name>; <name><surname>Li</surname><given-names>Y.</given-names></name> (<year>2004</year>) <article-title>Structure-switching signaling aptamers: transducing molecular recognition
into fluorescence signaling</article-title>. <source>Chem.—Eur.
J.</source><volume>10</volume>, <fpage>1868</fpage>–<lpage>1876</lpage>.<pub-id pub-id-type="pmid">15079825</pub-id></mixed-citation></ref><ref id="ref26"><mixed-citation publication-type="journal" id="cit26"><name><surname>Nutiu</surname><given-names>R.</given-names></name>; <name><surname>Li</surname><given-names>Y.</given-names></name> (<year>2003</year>) <article-title>Structure-switching
signaling aptamers</article-title>. <source>J.
Am. Chem. Soc.</source><volume>125</volume>, <fpage>4771</fpage>–<lpage>4778</lpage>.<pub-id pub-id-type="pmid">12696895</pub-id></mixed-citation></ref><ref id="ref27"><mixed-citation publication-type="journal" id="cit27"><name><surname>Friedman</surname><given-names>A. E.</given-names></name>; <name><surname>Chambron</surname><given-names>J. C.</given-names></name>; <name><surname>Sauvage</surname><given-names>J. P.</given-names></name>; <name><surname>Turro</surname><given-names>N. J.</given-names></name>; <name><surname>Barton</surname><given-names>J. K.</given-names></name> (<year>1990</year>) <article-title>Molecular
″light switch″ for DNA: Ru(bpy)<sub>2</sub>(dppz)<sup>2+</sup></article-title>. <source>J. Am. Chem. Soc.</source><volume>112</volume>, <fpage>4960</fpage>–<lpage>4962</lpage>.</mixed-citation></ref><ref id="ref28"><mixed-citation publication-type="journal" id="cit28"><name><surname>Holmlin</surname><given-names>R. E.</given-names></name>; <name><surname>Yao</surname><given-names>J. A.</given-names></name>; <name><surname>Barton</surname><given-names>J. K.</given-names></name> (<year>1999</year>) <article-title>Dipyridophenazine
complexes of Os(II)
as red-emitting DNA probes: synthesis, characterization, and photophysical
properties</article-title>. <source>Inorg. Chem.</source><volume>38</volume>, <fpage>174</fpage>–<lpage>189</lpage>.</mixed-citation></ref><ref id="ref29"><mixed-citation publication-type="journal" id="cit29"><name><surname>Chan</surname><given-names>D. S.-H.</given-names></name>; <name><surname>Lee</surname><given-names>H.-M.</given-names></name>; <name><surname>Che</surname><given-names>C.-M.</given-names></name>; <name><surname>Leung</surname><given-names>C.-H.</given-names></name>; <name><surname>Ma</surname><given-names>D.-L.</given-names></name> (<year>2009</year>) <article-title>A selective
oligonucleotide-based luminescent switch-on probe for the detection
of nanomolar mercury(II) ion in aqueous solution</article-title>. <source>Chem. Commun.</source><fpage>7479</fpage>–<lpage>7481</lpage>.</mixed-citation></ref><ref id="ref30"><mixed-citation publication-type="journal" id="cit30"><name><surname>Liu</surname><given-names>H.-K.</given-names></name>; <name><surname>Sadler</surname><given-names>P. J.</given-names></name> (<year>2011</year>) <article-title>Metal complexes
as DNA intercalators</article-title>. <source>Acc. Chem. Res.</source><volume>44</volume>, <fpage>349</fpage>–<lpage>359</lpage>.<pub-id pub-id-type="pmid">21446672</pub-id></mixed-citation></ref><ref id="ref31"><mixed-citation publication-type="journal" id="cit31"><name><surname>Larsen</surname><given-names>R. W.</given-names></name>; <name><surname>Jasuja</surname><given-names>R.</given-names></name>; <name><surname>Hetzler</surname><given-names>R. K.</given-names></name>; <name><surname>Muraoka</surname><given-names>P. T.</given-names></name>; <name><surname>Andrada</surname><given-names>V. G.</given-names></name>; <name><surname>Jameson</surname><given-names>D. M.</given-names></name> (<year>1996</year>) <article-title>Spectroscopic and
molecular modeling studies of caffeine
complexes with DNA intercalators</article-title>. <source>Biophys. J.</source><volume>70</volume>, <fpage>443</fpage>–<lpage>452</lpage>.<pub-id pub-id-type="pmid">8770220</pub-id></mixed-citation></ref><ref id="ref32"><mixed-citation publication-type="journal" id="cit32"><name><surname>Smolensky</surname><given-names>E. D.</given-names></name>; <name><surname>Peterson</surname><given-names>K. L.</given-names></name>; <name><surname>Weitz</surname><given-names>E. A.</given-names></name>; <name><surname>Lewandowski</surname><given-names>C.</given-names></name>; <name><surname>Pierre</surname><given-names>V. C.</given-names></name> (<year>2013</year>) <article-title>Magnetoluminescent light switches
- dual modality in
DNA detection</article-title>. <source>J. Am. Chem. Soc.</source><volume>135</volume>, <fpage>8966</fpage>–<lpage>8972</lpage>.<pub-id pub-id-type="pmid">23692333</pub-id></mixed-citation></ref><ref id="ref33"><mixed-citation publication-type="journal" id="cit33"><name><surname>Weitz</surname><given-names>E. A.</given-names></name>; <name><surname>Chang</surname><given-names>J. Y.</given-names></name>; <name><surname>Rosenfield</surname><given-names>A. H.</given-names></name>; <name><surname>Pierre</surname><given-names>V. C.</given-names></name> (<year>2012</year>) <article-title>A selective luminescent
sensor for the time-gated detection of ATP</article-title>. <source>J. Am. Chem. Soc.</source><volume>134</volume>, <fpage>16099</fpage>–<lpage>16102</lpage>.<pub-id pub-id-type="pmid">22994413</pub-id></mixed-citation></ref><ref id="ref34"><mixed-citation publication-type="journal" id="cit34"><name><surname>Bobba</surname><given-names>G.</given-names></name>; <name><surname>Bretonniere</surname><given-names>Y.</given-names></name>; <name><surname>Frias</surname><given-names>J. C.</given-names></name>; <name><surname>Parker</surname><given-names>D.</given-names></name> (<year>2003</year>) <article-title>Enantiopure lanthanide
complexes incorporating a tetraazatriphenylene sensitiser and three
naphthyl groups: exciton coupling, intramolecular energy transfer,
efficient singlet oxygen formation and perturbation by DNA binding</article-title>. <source>Org. Biomol. Chem.</source><volume>1</volume>, <fpage>1870</fpage>–<lpage>1872</lpage>.<pub-id pub-id-type="pmid">12945767</pub-id></mixed-citation></ref><ref id="ref35"><mixed-citation publication-type="journal" id="cit35"><name><surname>Bobba</surname><given-names>G.</given-names></name>; <name><surname>Dickins</surname><given-names>R. S.</given-names></name>; <name><surname>Kean</surname><given-names>S. D.</given-names></name>; <name><surname>Mathieu</surname><given-names>C. E.</given-names></name>; <name><surname>Parker</surname><given-names>D.</given-names></name>; <name><surname>Peacock</surname><given-names>R. D.</given-names></name>; <name><surname>Siligardi</surname><given-names>G.</given-names></name>; <name><surname>Smith</surname><given-names>M. J.</given-names></name>; <name><surname>Gareth
Williams</surname><given-names>J. A.</given-names></name>; <name><surname>Geraldes</surname><given-names>C. F. G. C.</given-names></name> (<year>2001</year>) <article-title>Chiroptical, ESMS and NMR spectroscopic
study of the interaction of enantiopure lanthanide complexes with
selected self-complementary dodecamer oligonucleotides</article-title>. <source>J. Chem. Soc., Perkin Trans.</source><volume>2</volume>, <fpage>1729</fpage>–<lpage>1737</lpage>.</mixed-citation></ref><ref id="ref36"><mixed-citation publication-type="journal" id="cit36"><name><surname>Bobba</surname><given-names>G.</given-names></name>; <name><surname>Frias</surname><given-names>J. C.</given-names></name>; <name><surname>Parker</surname><given-names>D.</given-names></name> (<year>2002</year>) <article-title>Highly emissive, nine-coordinate
enantiopure lanthanide complexes incorporating tetraazatriphenylenes
as probes for DNA</article-title>. <source>Chem. Commun.</source><fpage>890</fpage>–<lpage>891</lpage>.</mixed-citation></ref><ref id="ref37"><mixed-citation publication-type="journal" id="cit37"><name><surname>Bobba</surname><given-names>G.</given-names></name>; <name><surname>Kean</surname><given-names>S. D.</given-names></name>; <name><surname>Parker</surname><given-names>D.</given-names></name>; <name><surname>Beeby</surname><given-names>A.</given-names></name>; <name><surname>Baker</surname><given-names>G.</given-names></name> (<year>2001</year>) <article-title>DNA binding
studies of cationic lanthanide complexes bearing a phenanthridinium
group</article-title>. <source>J. Chem. Soc., Perkin Trans.</source><volume>2</volume>, <fpage>1738</fpage>–<lpage>1741</lpage>.</mixed-citation></ref><ref id="ref38"><mixed-citation publication-type="journal" id="cit38"><name><surname>Cacheris</surname><given-names>W. P.</given-names></name>; <name><surname>Quay</surname><given-names>S. C.</given-names></name>; <name><surname>Rocklage</surname><given-names>S. M.</given-names></name> (<year>1990</year>) <article-title>The relationship
between thermodynamics
and the toxicity of gadolinium complexes</article-title>. <source>Magn.
Res. Imaging</source><volume>8</volume>, <fpage>467</fpage>–<lpage>481</lpage>.</mixed-citation></ref><ref id="ref39"><mixed-citation publication-type="journal" id="cit39"><name><surname>Hermann</surname><given-names>P.</given-names></name>; <name><surname>Kotek</surname><given-names>J.</given-names></name>; <name><surname>Kubicek</surname><given-names>V.</given-names></name>; <name><surname>Lukes</surname><given-names>I.</given-names></name> (<year>2008</year>) <article-title>Gadolinium(iii) complexes
as MRI contrast agents: ligand design and properties of the complexes</article-title>. <source>Dalton Trans.</source><fpage>3027</fpage>–<lpage>3047</lpage>.<pub-id pub-id-type="pmid">18521444</pub-id></mixed-citation></ref><ref id="ref40"><mixed-citation publication-type="journal" id="cit40"><name><surname>Wang</surname><given-names>Z.</given-names></name>; <name><surname>Heon Lee</surname><given-names>J.</given-names></name>; <name><surname>Lu</surname><given-names>Y.</given-names></name> (<year>2008</year>) <article-title>Highly sensitive
″turn-on″
fluorescent sensor for Hg<sup>2+</sup> in aqueous solution based on
structure-switching DNA</article-title>. <source>Chem. Commun.</source><fpage>6005</fpage>–<lpage>6007</lpage>.</mixed-citation></ref><ref id="ref41"><mixed-citation publication-type="journal" id="cit41"><name><surname>Kovacs</surname><given-names>Z.</given-names></name>; <name><surname>Sherry</surname><given-names>A. D.</given-names></name> (<year>1997</year>) <article-title>pH-controlled selective protection
of polyaza macrocycles</article-title>. <source>Synthesis</source><volume>1997</volume>, <fpage>759</fpage>–<lpage>763</lpage>.</mixed-citation></ref><ref id="ref42"><mixed-citation publication-type="journal" id="cit42"><name><surname>Moreau</surname><given-names>J.</given-names></name>; <name><surname>Guillon</surname><given-names>E.</given-names></name>; <name><surname>Pierrard</surname><given-names>J. C.</given-names></name>; <name><surname>Rimbault</surname><given-names>J.</given-names></name>; <name><surname>Port</surname><given-names>M.</given-names></name>; <name><surname>Aplincourt</surname><given-names>M.</given-names></name> (<year>2004</year>) <article-title>Complexing
mechanism of the lanthanide cations Eu<sup>3+</sup>, Gd<sup>3+</sup>, and Tb<sup>3+</sup> with 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane
(DOTA) - characterization of three successive complexing phases: study
of the thermodynamic and structural properties of the complexes by
potentiometry, luminescence spectroscopy, and EXAFS</article-title>. <source>Chem.—Eur. J.</source><volume>10</volume>, <fpage>5218</fpage>–<lpage>5232</lpage>.<pub-id pub-id-type="pmid">15372580</pub-id></mixed-citation></ref><ref id="ref43"><mixed-citation publication-type="journal" id="cit43"><name><surname>Magda</surname><given-names>D.</given-names></name>; <name><surname>Wright</surname><given-names>M.</given-names></name>; <name><surname>Crofts</surname><given-names>S.</given-names></name>; <name><surname>Lin</surname><given-names>A.</given-names></name>; <name><surname>Sessler</surname><given-names>J. L.</given-names></name> (<year>1997</year>) <article-title>Metal complex
conjugates of antisense DNA which display ribozyme-like activity</article-title>. <source>J. Am. Chem. Soc.</source><volume>119</volume>, <fpage>6947</fpage>–<lpage>6948</lpage>.</mixed-citation></ref><ref id="ref44"><mixed-citation publication-type="journal" id="cit44"><name><surname>Holmlin</surname><given-names>R. E.</given-names></name>; <name><surname>Dandliker</surname><given-names>P. J.</given-names></name>; <name><surname>Barton</surname><given-names>J. K.</given-names></name> (<year>1999</year>) <article-title>Synthesis of metallointercalator-DNA
conjugates on a solid support</article-title>. <source>Bioconjugate
Chem.</source><volume>10</volume>, <fpage>1122</fpage>–<lpage>1130</lpage>.</mixed-citation></ref><ref id="ref45"><mixed-citation publication-type="journal" id="cit45"><name><surname>Gaballah</surname><given-names>S.
T.</given-names></name>; <name><surname>Kerr</surname><given-names>C. E.</given-names></name>; <name><surname>Eaton</surname><given-names>B. E.</given-names></name>; <name><surname>Netzel</surname><given-names>T. L.</given-names></name> (<year>2002</year>) <article-title>Synthesis of 5-(2,2′-bipyridinyl
and 2,2′-bipyridinediiumyl)-2′-deoxyuridine nucleosides:
precursors to metallo-DNA conjugates</article-title>. <source>Nucleosides
Nucleotides Nucleic Acids</source><volume>21</volume>, <fpage>547</fpage>–<lpage>560</lpage>.<pub-id pub-id-type="pmid">12484450</pub-id></mixed-citation></ref><ref id="ref46"><mixed-citation publication-type="journal" id="cit46"><name><surname>Hara</surname><given-names>K.</given-names></name>; <name><surname>Kitamura</surname><given-names>M.</given-names></name>; <name><surname>Inoue</surname><given-names>H.</given-names></name> (<year>2004</year>) <article-title>Synthesis and hybridization studies
on oligonucleotide-metal complex conjugates</article-title>. <source>Nucleic Acids Symp. Ser.</source><fpage>217</fpage>–<lpage>218</lpage>.</mixed-citation></ref><ref id="ref47"><mixed-citation publication-type="journal" id="cit47"><name><surname>Ihara</surname><given-names>T.</given-names></name>; <name><surname>Kitamura</surname><given-names>Y.</given-names></name>; <name><surname>Okada</surname><given-names>K.</given-names></name>; <name><surname>Tazaki</surname><given-names>M.</given-names></name>; <name><surname>Jyo</surname><given-names>A.</given-names></name> (<year>2005</year>) <article-title>Asymmetric
cooperativity in tandem hybridization of the DNA conjugates bearing
chiral metal complexes</article-title>. <source>Nucleic Acids Symp.
Ser.</source><fpage>229</fpage>–<lpage>230</lpage>.</mixed-citation></ref><ref id="ref48"><mixed-citation publication-type="journal" id="cit48"><name><surname>Graf</surname><given-names>N.</given-names></name>; <name><surname>Goritz</surname><given-names>M.</given-names></name>; <name><surname>Kramer</surname><given-names>R.</given-names></name> (<year>2006</year>) <article-title>A metal-ion-releasing
probe for DNA
detection by catalytic signal amplification</article-title>. <source>Angew. Chem., Int. Ed. Engl.</source><volume>45</volume>, <fpage>4013</fpage>–<lpage>4015</lpage>.<pub-id pub-id-type="pmid">16683284</pub-id></mixed-citation></ref><ref id="ref49"><mixed-citation publication-type="journal" id="cit49"><name><surname>Kitamura</surname><given-names>Y.</given-names></name>; <name><surname>Ihara</surname><given-names>T.</given-names></name>; <name><surname>Tsujimura</surname><given-names>Y.</given-names></name>; <name><surname>Osawa</surname><given-names>Y.</given-names></name>; <name><surname>Jyo</surname><given-names>A.</given-names></name> (<year>2006</year>) <article-title>Colorimetric
allele analysis based on the DNA-directed cooperative formation of
luminous lanthanide complexes</article-title>. <source>Nucleic Acids
Symp. Ser.</source><fpage>105</fpage>–<lpage>106</lpage>.</mixed-citation></ref><ref id="ref50"><mixed-citation publication-type="journal" id="cit50"><name><surname>Dubey</surname><given-names>I. Y.</given-names></name>; <name><surname>Dubey</surname><given-names>L. V.</given-names></name>; <name><surname>Piletska</surname><given-names>E. V.</given-names></name>; <name><surname>Piletsky</surname><given-names>S. A.</given-names></name> (<year>2007</year>) <article-title>Metal complexes
of 1,4,7-triazacyclononane and their oligonucleotide conjugates as
chemical nucleases</article-title>. <source>Ukrainica Bioorganica Acta</source><volume>5</volume>, <fpage>11</fpage>–<lpage>19</lpage>.</mixed-citation></ref><ref id="ref51"><mixed-citation publication-type="journal" id="cit51"><name><surname>Andersen</surname><given-names>C. S.</given-names></name>; <name><surname>Yan</surname><given-names>H.</given-names></name>; <name><surname>Gothelf</surname><given-names>K. V.</given-names></name> (<year>2008</year>) <article-title>Bridging
one helical turn in double-stranded DNA by
templated dimerization of molecular rods</article-title>. <source>Angew.
Chem., Int. Ed. Engl.</source><volume>47</volume>, <fpage>5569</fpage>–<lpage>5572</lpage>.<pub-id pub-id-type="pmid">18574842</pub-id></mixed-citation></ref><ref id="ref52"><mixed-citation publication-type="journal" id="cit52"><name><surname>Ghosh</surname><given-names>S.</given-names></name>; <name><surname>Pignot-Paintrand</surname><given-names>I.</given-names></name>; <name><surname>Dumy</surname><given-names>P.</given-names></name>; <name><surname>Defrancq</surname><given-names>E.</given-names></name> (<year>2009</year>) <article-title>Design and synthesis
of novel hybrid metal complex-DNA conjugates: key building blocks
for multimetallic linear DNA nanoarrays</article-title>. <source>Org.
Biomol. Chem.</source><volume>7</volume>, <fpage>2729</fpage>–<lpage>2737</lpage>.<pub-id pub-id-type="pmid">19532989</pub-id></mixed-citation></ref><ref id="ref53"><mixed-citation publication-type="journal" id="cit53"><name><surname>Ihara</surname><given-names>T.</given-names></name>; <name><surname>Kitamura</surname><given-names>Y.</given-names></name>; <name><surname>Tsujimura</surname><given-names>Y.</given-names></name>; <name><surname>Jyo</surname><given-names>A.</given-names></name> (<year>2011</year>) <article-title>DNA analysis based
on the local structural disruption to the duplexes carrying a luminous
lanthanide complex</article-title>. <source>Anal. Sci.</source><volume>27</volume>, <fpage>585</fpage>–<lpage>590</lpage>.<pub-id pub-id-type="pmid">21666354</pub-id></mixed-citation></ref><ref id="ref54"><mixed-citation publication-type="journal" id="cit54"><name><surname>Hurtado</surname><given-names>R. R.</given-names></name>; <name><surname>Harney</surname><given-names>A. S.</given-names></name>; <name><surname>Heffern</surname><given-names>M. C.</given-names></name>; <name><surname>Holbrook</surname><given-names>R. J.</given-names></name>; <name><surname>Holmgren</surname><given-names>R. A.</given-names></name>; <name><surname>Meade</surname><given-names>T. J.</given-names></name> (<year>2012</year>) <article-title>Specific inhibition
of the transcription factor Ci
by a cobalt(III) Schiff base-DNA conjugate</article-title>. <source>Mol. Pharmaceutics</source><volume>9</volume>, <fpage>325</fpage>–<lpage>333</lpage>.</mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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