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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Labeling of Adenovirus Particles with PARACEST Agents</title><author><name sortKey="Vasalatiy, Olga" sort="Vasalatiy, Olga" uniqKey="Vasalatiy O" first="Olga" last="Vasalatiy">Olga Vasalatiy</name><affiliation><nlm:aff id="A1">Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, Texas 75083</nlm:aff></affiliation></author><author><name sortKey="Gerard, Robert D" sort="Gerard, Robert D" uniqKey="Gerard R" first="Robert D" last="Gerard">Robert D. Gerard</name><affiliation><nlm:aff id="A2">Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390</nlm:aff></affiliation></author><author><name sortKey="Zhao, Piyu" sort="Zhao, Piyu" uniqKey="Zhao P" first="Piyu" last="Zhao">Piyu Zhao</name><affiliation><nlm:aff id="A1">Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, Texas 75083</nlm:aff></affiliation></author><author><name sortKey="Sun, Xiankai" sort="Sun, Xiankai" uniqKey="Sun X" first="Xiankai" last="Sun">Xiankai Sun</name><affiliation><nlm:aff id="A3">Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390</nlm:aff></affiliation></author><author><name sortKey="Sherry, A Dean" sort="Sherry, A Dean" uniqKey="Sherry A" first="A. Dean" last="Sherry">A. Dean Sherry</name><affiliation><nlm:aff id="A1">Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, Texas 75083</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, NE 4.2, Dallas, Texas 75390</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18254605</idno><idno type="pmc">2696891</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696891</idno><idno type="RBID">PMC:2696891</idno><idno type="doi">10.1021/bc7002605</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000236</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000236</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Labeling of Adenovirus Particles with PARACEST Agents</title><author><name sortKey="Vasalatiy, Olga" sort="Vasalatiy, Olga" uniqKey="Vasalatiy O" first="Olga" last="Vasalatiy">Olga Vasalatiy</name><affiliation><nlm:aff id="A1">Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, Texas 75083</nlm:aff></affiliation></author><author><name sortKey="Gerard, Robert D" sort="Gerard, Robert D" uniqKey="Gerard R" first="Robert D" last="Gerard">Robert D. Gerard</name><affiliation><nlm:aff id="A2">Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390</nlm:aff></affiliation></author><author><name sortKey="Zhao, Piyu" sort="Zhao, Piyu" uniqKey="Zhao P" first="Piyu" last="Zhao">Piyu Zhao</name><affiliation><nlm:aff id="A1">Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, Texas 75083</nlm:aff></affiliation></author><author><name sortKey="Sun, Xiankai" sort="Sun, Xiankai" uniqKey="Sun X" first="Xiankai" last="Sun">Xiankai Sun</name><affiliation><nlm:aff id="A3">Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390</nlm:aff></affiliation></author><author><name sortKey="Sherry, A Dean" sort="Sherry, A Dean" uniqKey="Sherry A" first="A. Dean" last="Sherry">A. Dean Sherry</name><affiliation><nlm:aff id="A1">Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, Texas 75083</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, NE 4.2, Dallas, Texas 75390</nlm:aff></affiliation></author></analytic><series><title level="j">Bioconjugate chemistry</title><idno type="ISSN">1043-1802</idno><idno type="eISSN">1520-4812</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Recombinant adenovirus type 5 particles (AdCMVLuc) were labeled with two different bifunctional ligands capable of forming stable complexes with paramagnetic lanthanide ions. The number of covalently attached ligands varied between 630 and 1960 per adenovirus particle depending upon the chemical reactivity of the bifunctional ligand (NHS ester versus isothiocyanide), the amount of excess ligand added, and the reaction time. The bioactivity of each labeled adenovirus derivative, as measured by the ability of the virus to infect cells and express luciferase, was shown to be highly dependent upon the number of covalently attached ligands. This indicates that certain amino groups, likely on the surface of the adenovirus fiber protein where cell binding is known to occur, are critical for viral attachment and infection. Addition of <sup>177</sup>Lu<sup>3+</sup> to chemically modified versus control viruses demonstrated a significant amount of nonspecific binding of <sup>177</sup>Lu<sup>3+</sup> to the virus particles that could not be sequestered by addition of excess DTPA. Thus, it became necessary to implement a prelabeling strategy for conjugation of preformed lanthanide ligand chelates to adenovirus particles. Using preformed Tm<sup>3+</sup>-<bold>L2</bold>, a large number of chelates having chemical exchange saturation transfer (CEST) properties were attached to the surface residues of AdCMVLuc without nonspecific binding of metal ions elsewhere on the virus particle. The potential of such conjugates to act as PARACEST imaging agents was tested using an on-resonance WALTZ sequence for CEST activation. A 12% decrease in bulk water signal intensity was observed relative to controls. This demonstrates that viral particles labeled with PARACEST-type imaging agents can potentially serve as targeted agents for molecular imaging.</p></div></front></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9010319</journal-id><journal-id journal-id-type="pubmed-jr-id">1061</journal-id><journal-id journal-id-type="nlm-ta">Bioconjug Chem</journal-id><journal-title>Bioconjugate chemistry</journal-title><issn pub-type="ppub">1043-1802</issn><issn pub-type="epub">1520-4812</issn></journal-meta><article-meta><article-id pub-id-type="pmid">18254605</article-id><article-id pub-id-type="pmc">2696891</article-id><article-id pub-id-type="manuscript">NIHMS108531</article-id><article-id pub-id-type="doi">10.1021/bc7002605</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Labeling of Adenovirus Particles with PARACEST Agents</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Vasalatiy</surname><given-names>Olga</given-names></name><xref ref-type="aff" rid="A1">†</xref></contrib><contrib contrib-type="author"><name><surname>Gerard</surname><given-names>Robert D</given-names></name><xref ref-type="aff" rid="A2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Piyu</given-names></name><xref ref-type="aff" rid="A1">†</xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Xiankai</given-names></name><xref ref-type="aff" rid="A3">§</xref></contrib><contrib contrib-type="author"><name><surname>Sherry</surname><given-names>A. Dean</given-names></name><xref ref-type="aff" rid="A1">†</xref><xref ref-type="aff" rid="A3">§</xref><xref ref-type="aff" rid="A4">‖</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="A1"><label>†</label>Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, Texas 75083</aff><aff id="A2"><label>‡</label>Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390</aff><aff id="A3"><label>§</label>Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390</aff><aff id="A4"><label>‖</label>Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, NE 4.2, Dallas, Texas 75390</aff><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed. Tel: (214) 645-2730, e-mail: <email>dean.sherry@utsouthwestern.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>9</day><month>4</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>7</day><month>2</month><year>2008</year></pub-date><pub-date pub-type="ppub"><month>3</month><year>2008</year></pub-date><pub-date pub-type="pmc-release"><day>16</day><month>6</month><year>2009</year></pub-date><volume>19</volume><issue>3</issue><fpage>598</fpage><lpage>606</lpage><permissions><copyright-statement>© 2008 American Chemical Society</copyright-statement><copyright-year>2008</copyright-year></permissions><abstract><p id="P1">Recombinant adenovirus type 5 particles (AdCMVLuc) were labeled with two different bifunctional ligands capable of forming stable complexes with paramagnetic lanthanide ions. The number of covalently attached ligands varied between 630 and 1960 per adenovirus particle depending upon the chemical reactivity of the bifunctional ligand (NHS ester versus isothiocyanide), the amount of excess ligand added, and the reaction time. The bioactivity of each labeled adenovirus derivative, as measured by the ability of the virus to infect cells and express luciferase, was shown to be highly dependent upon the number of covalently attached ligands. This indicates that certain amino groups, likely on the surface of the adenovirus fiber protein where cell binding is known to occur, are critical for viral attachment and infection. Addition of <sup>177</sup>Lu<sup>3+</sup> to chemically modified versus control viruses demonstrated a significant amount of nonspecific binding of <sup>177</sup>Lu<sup>3+</sup> to the virus particles that could not be sequestered by addition of excess DTPA. Thus, it became necessary to implement a prelabeling strategy for conjugation of preformed lanthanide ligand chelates to adenovirus particles. Using preformed Tm<sup>3+</sup>-<bold>L2</bold>, a large number of chelates having chemical exchange saturation transfer (CEST) properties were attached to the surface residues of AdCMVLuc without nonspecific binding of metal ions elsewhere on the virus particle. The potential of such conjugates to act as PARACEST imaging agents was tested using an on-resonance WALTZ sequence for CEST activation. A 12% decrease in bulk water signal intensity was observed relative to controls. This demonstrates that viral particles labeled with PARACEST-type imaging agents can potentially serve as targeted agents for molecular imaging.</p></abstract><contract-num rid="CA1">R01 CA115531-02</contract-num><contract-num rid="RR1">P41 RR002584-216319</contract-num><contract-sponsor id="CA1">National Cancer Institute : NCI</contract-sponsor><contract-sponsor id="RR1">National Center for Research Resources : NCRR</contract-sponsor></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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