TY - JOUR
T1 - Nucleic acids targeted to drugs
T2 - SELEX against a quadruplex ligand
AU - Renaud De La Faverie, Amandine
AU - Hamon, Florian
AU - Di Primo, Carmelo
AU - Largy, Eric
AU - Dausse, Eric
AU - Delaurire, Laurence
AU - Landras-Guetta, Corinne
AU - Toulmé, Jean Jacques
AU - Teulade-Fichou, Marie Paule
AU - Mergny, Jean Louis
N1 - Funding Information:
We thank members of the Mergny, Toulmé and Teulade-Fichou laboratories for helpful discussions. This work was supported by an ANR grant (G4-TOOLBOX, ANR-Blan-09-355) to J.L.M., M.P.T.F. and J.J.T. A.R.F. is the recipient of an Université Bordeaux Segalen – MESR PhD studentship. J.L.M. acknowledges support from the Région Aquitaine, the Fondation pour la Recherche Médicale (F.R.M.), and INCa and wishes to dedicate this article to the memory of G. Cherruault – a friend reaped by a Katana we still cannot always parry.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - 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.
AB - 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.
KW - Aptamer
KW - Drug-DNA interactions
KW - Quadruplexes
KW - SELEX
KW - SPR
KW - Unusual nucleic acids structure
U2 - 10.1016/j.biochi.2011.05.022
DO - 10.1016/j.biochi.2011.05.022
M3 - Article
C2 - 21664224
AN - SCOPUS:79960700836
SN - 0300-9084
VL - 93
SP - 1357
EP - 1367
JO - Biochimie
JF - Biochimie
IS - 8
ER -