title: Photo-cross-linking probes for trapping G-quadruplex DNA.
abstract: We have developed a straightforward synthetic pathway to a set of six photoactivatable G-quadruplex ligands with a validated G4-binding motif (the bisquinolinium pyridodicarboxamide PDC-360A) tethered through various spacers to two different photo-cross-linking groups: benzophenone and an aryl azide. The high quadruplex-versus-duplex selectivity of the PDC core was retained in the new derivatives and resulted in selective alkylation of two well-known G-quadruplexes (human telomeric G4 and oncogene promoter c-myc G4) under conditions of harsh competition. The presence of two structurally different photoactivatable functions allowed the selective alkylation of G-quadruplex structures at specific nucleobases and irreversible G4 binding. The topology and sequence of the quadruplex matrix appear to influence strongly the alkylation profile, which differs for the telomeric and c-myc quadruplexes. The new compounds are photoactive in cells and thus provide new tools for studying G4 biology.
authors: Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110-112, 91405 Orsay (France) http://umr176.curie.fr/en/MPTF.
authors: Daniela
authors: D
authors: Verga
authors: Florian
authors: F
authors: Hamon
authors: Florent
authors: F
authors: Poyer
authors: Sophie
authors: S
authors: Bombard
authors: Marie-Paule
authors: MP
authors: Teulade-Fichou
mesh_terms: D001386:Azides / Q000737:chemistry*; D001577:Benzophenones / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D055668:Photochemical Processes
chemical_list: D001386:Azides; D001577:Benzophenones; D003432:Cross-Linking Reagents; D008024:Ligands; C047723:benzophenone
keywords: DNA; G-quadruplexes; alkylation; photo-cross-linking; photoactivatable probes