Nucleic acids targeted to drugs: SELEX against a quadruplex ligand
A number of small molecules demonstrate selective recognition of G-quadruplexes and are able to stabilize their formation. In this work, we performed the synthesis of two biotin-tagged G4 ligands and analyzed their interactions with DNA by two complementary techniques, FRET and FID. The compound tha...
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| Veröffentlicht in: | Biochimie 2011-08, Vol.93 (8), p.1357-1367 |
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| creator | Renaud de la Faverie, Amandine Hamon, Florian Di Primo, Carmelo Largy, Eric Dausse, Eric Delaurière, Laurence Landras-Guetta, Corinne Toulmé, Jean-Jacques Teulade-Fichou, Marie-Paule Mergny, Jean-Louis |
| description | A number of small molecules demonstrate selective recognition of G-quadruplexes and are able to stabilize their formation. In this work, we performed the synthesis of two biotin-tagged G4 ligands and analyzed their interactions with DNA by two complementary techniques, FRET and FID. The compound that exhibited the best characteristics (a biotin pyridocarboxamide derivative with high stabilization of an intramolecular quadruplex and excellent duplex–quadruplex specificity) was used as bait for
in vitro selection (SELEX). Among 80 DNA aptamer sequences selected, only a small minority (5/80) exhibited G4-prone motifs. Binding of consensus candidates was confirmed by SPR. These results indicate that G4 ligands that appear highly specific when comparing affinities or stabilization for one quadruplex against
one duplex, do not only bind quadruplex sequences but may also recognize other nucleic motifs as well. This observation may be relevant when whole genome or transcriptome analysis of binding sites is seeked for, as unexpected binding sites may also be present.
► We performed the synthesis of two biotin-tagged G4 ligands and analyzed their interactions with DNA. ► The compound that exhibited the best characteristics was used as bait for
in vitro selection (SELEX). ► Among 80 DNA aptamer sequences selected, only a small minority (5/80) exhibited G4-prone motifs. |
| doi_str_mv | 10.1016/j.biochi.2011.05.022 |
| format | Article |
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in vitro selection (SELEX). Among 80 DNA aptamer sequences selected, only a small minority (5/80) exhibited G4-prone motifs. Binding of consensus candidates was confirmed by SPR. These results indicate that G4 ligands that appear highly specific when comparing affinities or stabilization for one quadruplex against
one duplex, do not only bind quadruplex sequences but may also recognize other nucleic motifs as well. This observation may be relevant when whole genome or transcriptome analysis of binding sites is seeked for, as unexpected binding sites may also be present.
► We performed the synthesis of two biotin-tagged G4 ligands and analyzed their interactions with DNA. ► The compound that exhibited the best characteristics was used as bait for
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in vitro selection (SELEX). Among 80 DNA aptamer sequences selected, only a small minority (5/80) exhibited G4-prone motifs. Binding of consensus candidates was confirmed by SPR. These results indicate that G4 ligands that appear highly specific when comparing affinities or stabilization for one quadruplex against
one duplex, do not only bind quadruplex sequences but may also recognize other nucleic motifs as well. This observation may be relevant when whole genome or transcriptome analysis of binding sites is seeked for, as unexpected binding sites may also be present.
► We performed the synthesis of two biotin-tagged G4 ligands and analyzed their interactions with DNA. ► The compound that exhibited the best characteristics was used as bait for
in vitro selection (SELEX). ► Among 80 DNA aptamer sequences selected, only a small minority (5/80) exhibited G4-prone motifs.</description><subject>Aptamer</subject><subject>Biotin - chemistry</subject><subject>Circular Dichroism</subject><subject>Copper - chemistry</subject><subject>Drug Design</subject><subject>Drug–DNA interactions</subject><subject>Fluorescence Resonance Energy Transfer</subject><subject>G-Quadruplexes</subject><subject>Intercalating Agents - chemistry</subject><subject>Ligands</subject><subject>Quadruplexes</subject><subject>SELEX</subject><subject>SELEX Aptamer Technique</subject><subject>SPR</subject><subject>Surface Plasmon Resonance</subject><subject>Unusual nucleic acids structure</subject><issn>0300-9084</issn><issn>1638-6183</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LAzEQhoMotlb_gUhunnadZJP98CBoqR9Q9KCCt5AmszVl222TXdF_79ZVj3qagXned-Ah5JhBzIClZ4t45mrz6mIOjMUgY-B8hwxZmuRRyvJklwwhAYgKyMWAHISwAAAJvNgnA87SVHAuhuTqvjUVOkO1cTbQRvs5NmhpU1Pr23k4p4-T6eSF6rl2q9BQTTet7i7rCt9p5eZ6ZQ_JXqmrgEffc0SerydP49to-nBzN76cRkbIook0s8hkWQhbSiFSaTBhotQlT2Yw490OZcqNzI3WmRWgJZfMlmiE1WBYLpMROe17177etBgatXTBYFXpFdZtUAVkLEt4kf1L5lnRKcy-OkVPGl-H4LFUa--W2n8oBmqrWS1Ur1ltNSuQqtPcxU6-H7SzJdrf0I_XDrjoAeyEvDn0KhiHK4PWeTSNsrX7-8Mn5DSOoA</recordid><startdate>20110801</startdate><enddate>20110801</enddate><creator>Renaud de la Faverie, Amandine</creator><creator>Hamon, Florian</creator><creator>Di Primo, Carmelo</creator><creator>Largy, Eric</creator><creator>Dausse, Eric</creator><creator>Delaurière, Laurence</creator><creator>Landras-Guetta, Corinne</creator><creator>Toulmé, Jean-Jacques</creator><creator>Teulade-Fichou, Marie-Paule</creator><creator>Mergny, Jean-Louis</creator><general>Elsevier Masson SAS</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TM</scope></search><sort><creationdate>20110801</creationdate><title>Nucleic acids targeted to drugs: SELEX against a quadruplex ligand</title><author>Renaud de la Faverie, Amandine ; 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In this work, we performed the synthesis of two biotin-tagged G4 ligands and analyzed their interactions with DNA by two complementary techniques, FRET and FID. The compound that exhibited the best characteristics (a biotin pyridocarboxamide derivative with high stabilization of an intramolecular quadruplex and excellent duplex–quadruplex specificity) was used as bait for
in vitro selection (SELEX). Among 80 DNA aptamer sequences selected, only a small minority (5/80) exhibited G4-prone motifs. Binding of consensus candidates was confirmed by SPR. These results indicate that G4 ligands that appear highly specific when comparing affinities or stabilization for one quadruplex against
one duplex, do not only bind quadruplex sequences but may also recognize other nucleic motifs as well. This observation may be relevant when whole genome or transcriptome analysis of binding sites is seeked for, as unexpected binding sites may also be present.
► We performed the synthesis of two biotin-tagged G4 ligands and analyzed their interactions with DNA. ► The compound that exhibited the best characteristics was used as bait for
in vitro selection (SELEX). ► Among 80 DNA aptamer sequences selected, only a small minority (5/80) exhibited G4-prone motifs.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>21664224</pmid><doi>10.1016/j.biochi.2011.05.022</doi><tpages>11</tpages></addata></record> |
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| identifier | ISSN: 0300-9084 |
| ispartof | Biochimie, 2011-08, Vol.93 (8), p.1357-1367 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Aptamer Biotin - chemistry Circular Dichroism Copper - chemistry Drug Design Drug–DNA interactions Fluorescence Resonance Energy Transfer G-Quadruplexes Intercalating Agents - chemistry Ligands Quadruplexes SELEX SELEX Aptamer Technique SPR Surface Plasmon Resonance Unusual nucleic acids structure |
| title | Nucleic acids targeted to drugs: SELEX against a quadruplex ligand |
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