Transcription factor decoy oligonucleotides modified with locked nucleic acids: an in vitro study to reconcile biostability with binding affinity
Identifieur interne : 000275 ( Istex/Curation ); précédent : 000274; suivant : 000276Transcription factor decoy oligonucleotides modified with locked nucleic acids: an in vitro study to reconcile biostability with binding affinity
Auteurs : Rita Crinelli ; Marzia Bianchi ; Lucia Gentilini ; Linda Palma ; Mads D. S Rensen [Danemark] ; Torsten Bryld [Danemark] ; Ravindra B. Babu [Danemark] ; Khalil Arar [France] ; Jesper Wengel [Danemark] ; Mauro Magnani [Italie]Source :
- Nucleic Acids Research [ 0305-1048 ] ; 2004.
Abstract
Double‐stranded oligonucleotides (ODNs) containing the consensus binding sequence of a transcription factor provide a rationally designed tool to manipulate gene expression at the transcriptional level by the decoy approach. However, modifications introduced into oligonucleotides to increase stability quite often do not guarantee that transcription factor affinity and/or specificity of recognition are retained. We have previously evaluated the use of locked nucleic acids (LNA) in the design of decoy molecules for the transcription factor κB. Oligo nucleotides containing LNA substitutions displayed high resistance to exo‐ and endonucleolytic degradation, with LNA–DNA mix‐mers being more stable than LNA–DNA–LNA gap‐mers. However, insertion of internal LNA bases resulted in a loss of affinity for the transcription factor. This latter effect apparently depended on positioning of the internal LNA substitutions. Indeed, here we demonstrate that intra‐ and inter‐strand positioning of internal LNAs has to be carefully considered to maintain affinity and achieve high stability, respectively. Unfortun ately, our data also indicate that LNA positioning is not the only parameter affecting transcription factor binding, the interference in part being dependent on the intrinsic conformational properties of this nucleotide analog. To circumvent this problem, the successful use of an α‐l‐ribo‐ configured LNA is demonstrated, indicating LNA–DNA–α‐l‐LNA molecules as promising new decoy agents.
Url:
DOI: 10.1093/nar/gkh503
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000275
Links to Exploration step
ISTEX:5DBF0CDACDC47D5139549426D6D2DEDE439DFEEFLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Transcription factor decoy oligonucleotides modified with locked nucleic acids: an in vitro study to reconcile biostability with binding affinity</title>
<author><name sortKey="Crinelli, Rita" sort="Crinelli, Rita" uniqKey="Crinelli R" first="Rita" last="Crinelli">Rita Crinelli</name>
</author>
<author><name sortKey="Bianchi, Marzia" sort="Bianchi, Marzia" uniqKey="Bianchi M" first="Marzia" last="Bianchi">Marzia Bianchi</name>
</author>
<author><name sortKey="Gentilini, Lucia" sort="Gentilini, Lucia" uniqKey="Gentilini L" first="Lucia" last="Gentilini">Lucia Gentilini</name>
</author>
<author><name sortKey="Palma, Linda" sort="Palma, Linda" uniqKey="Palma L" first="Linda" last="Palma">Linda Palma</name>
</author>
<author><name sortKey="S Rensen, Mads D" sort="S Rensen, Mads D" uniqKey="S Rensen M" first="Mads D." last="S Rensen">Mads D. S Rensen</name>
<affiliation wicri:level="1"><mods:affiliation>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M, Denmark and</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bryld, Torsten" sort="Bryld, Torsten" uniqKey="Bryld T" first="Torsten" last="Bryld">Torsten Bryld</name>
<affiliation wicri:level="1"><mods:affiliation>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M, Denmark and</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Babu, Ravindra B" sort="Babu, Ravindra B" uniqKey="Babu R" first="Ravindra B." last="Babu">Ravindra B. Babu</name>
<affiliation wicri:level="1"><mods:affiliation>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M, Denmark and</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Arar, Khalil" sort="Arar, Khalil" uniqKey="Arar K" first="Khalil" last="Arar">Khalil Arar</name>
<affiliation wicri:level="1"><mods:affiliation>Proligo LLC, 1 Rue Delaunay, 75011 Paris, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Proligo LLC, 1 Rue Delaunay, 75011 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wengel, Jesper" sort="Wengel, Jesper" uniqKey="Wengel J" first="Jesper" last="Wengel">Jesper Wengel</name>
<affiliation wicri:level="1"><mods:affiliation>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M, Denmark and</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Magnani, Mauro" sort="Magnani, Mauro" uniqKey="Magnani M" first="Mauro" last="Magnani">Mauro Magnani</name>
<affiliation wicri:level="1"><mods:affiliation>*To whom correspondence should be addressed. Tel: +39 0722 305211; Fax: +39 0722 320188; Email: magnani@uniurb.it</mods:affiliation>
<country wicri:rule="url">Italie</country>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:5DBF0CDACDC47D5139549426D6D2DEDE439DFEEF</idno>
<date when="2004" year="2004">2004</date>
<idno type="doi">10.1093/nar/gkh503</idno>
<idno type="url">https://api.istex.fr/ark:/67375/HXZ-4DSVQ0HL-1/fulltext.pdf</idno>
<idno type="wicri:Area/Istex/Corpus">000275</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000275</idno>
<idno type="wicri:Area/Istex/Curation">000275</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a" type="main">Transcription factor decoy oligonucleotides modified with locked nucleic acids: an <hi rend="italic">in vitro</hi>
study to reconcile biostability with binding affinity</title>
<author><name sortKey="Crinelli, Rita" sort="Crinelli, Rita" uniqKey="Crinelli R" first="Rita" last="Crinelli">Rita Crinelli</name>
</author>
<author><name sortKey="Bianchi, Marzia" sort="Bianchi, Marzia" uniqKey="Bianchi M" first="Marzia" last="Bianchi">Marzia Bianchi</name>
</author>
<author><name sortKey="Gentilini, Lucia" sort="Gentilini, Lucia" uniqKey="Gentilini L" first="Lucia" last="Gentilini">Lucia Gentilini</name>
</author>
<author><name sortKey="Palma, Linda" sort="Palma, Linda" uniqKey="Palma L" first="Linda" last="Palma">Linda Palma</name>
</author>
<author><name sortKey="S Rensen, Mads D" sort="S Rensen, Mads D" uniqKey="S Rensen M" first="Mads D." last="S Rensen">Mads D. S Rensen</name>
<affiliation wicri:level="1"><mods:affiliation>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M, Denmark and</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bryld, Torsten" sort="Bryld, Torsten" uniqKey="Bryld T" first="Torsten" last="Bryld">Torsten Bryld</name>
<affiliation wicri:level="1"><mods:affiliation>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M, Denmark and</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Babu, Ravindra B" sort="Babu, Ravindra B" uniqKey="Babu R" first="Ravindra B." last="Babu">Ravindra B. Babu</name>
<affiliation wicri:level="1"><mods:affiliation>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M, Denmark and</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Arar, Khalil" sort="Arar, Khalil" uniqKey="Arar K" first="Khalil" last="Arar">Khalil Arar</name>
<affiliation wicri:level="1"><mods:affiliation>Proligo LLC, 1 Rue Delaunay, 75011 Paris, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Proligo LLC, 1 Rue Delaunay, 75011 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wengel, Jesper" sort="Wengel, Jesper" uniqKey="Wengel J" first="Jesper" last="Wengel">Jesper Wengel</name>
<affiliation wicri:level="1"><mods:affiliation>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M, Denmark and</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK‐5230 Odense M</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Magnani, Mauro" sort="Magnani, Mauro" uniqKey="Magnani M" first="Mauro" last="Magnani">Mauro Magnani</name>
<affiliation wicri:level="1"><mods:affiliation>*To whom correspondence should be addressed. Tel: +39 0722 305211; Fax: +39 0722 320188; Email: magnani@uniurb.it</mods:affiliation>
<country wicri:rule="url">Italie</country>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j" type="main">Nucleic Acids Research</title>
<title level="j" type="abbrev">Nucl. Acids Res.</title>
<idno type="ISSN">0305-1048</idno>
<idno type="eISSN">1362-4962</idno>
<imprint><publisher>Oxford University Press</publisher>
<date type="published">2004</date>
<biblScope unit="vol">32</biblScope>
<biblScope unit="issue">6</biblScope>
<biblScope unit="page" from="1874">1874</biblScope>
<biblScope unit="page" to="1885">1885</biblScope>
</imprint>
<idno type="ISSN">0305-1048</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0305-1048</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Double‐stranded oligonucleotides (ODNs) containing the consensus binding sequence of a transcription factor provide a rationally designed tool to manipulate gene expression at the transcriptional level by the decoy approach. However, modifications introduced into oligonucleotides to increase stability quite often do not guarantee that transcription factor affinity and/or specificity of recognition are retained. We have previously evaluated the use of locked nucleic acids (LNA) in the design of decoy molecules for the transcription factor κB. Oligo nucleotides containing LNA substitutions displayed high resistance to exo‐ and endonucleolytic degradation, with LNA–DNA mix‐mers being more stable than LNA–DNA–LNA gap‐mers. However, insertion of internal LNA bases resulted in a loss of affinity for the transcription factor. This latter effect apparently depended on positioning of the internal LNA substitutions. Indeed, here we demonstrate that intra‐ and inter‐strand positioning of internal LNAs has to be carefully considered to maintain affinity and achieve high stability, respectively. Unfortun ately, our data also indicate that LNA positioning is not the only parameter affecting transcription factor binding, the interference in part being dependent on the intrinsic conformational properties of this nucleotide analog. To circumvent this problem, the successful use of an α‐l‐ribo‐ configured LNA is demonstrated, indicating LNA–DNA–α‐l‐LNA molecules as promising new decoy agents.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Istex/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000275 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Curation/biblio.hfd -nk 000275 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= MersV1 |flux= Istex |étape= Curation |type= RBID |clé= ISTEX:5DBF0CDACDC47D5139549426D6D2DEDE439DFEEF |texte= Transcription factor decoy oligonucleotides modified with locked nucleic acids: an in vitro study to reconcile biostability with binding affinity }}
![]() | This area was generated with Dilib version V0.6.33. | ![]() |