title: Exclusive platination of loop adenines in the human telomeric G-quadruplex.
abstract: The present article reports on the platination of the human telomeric G-quadruplex by three Pt-terpyridine complexes. It is shown that extension of the aromatic surface of the terpyridine moiety surrounding the platinum atom influences both the binding affinity and the platination activity. Remarkably, the most strongly bound complex Pt-ttpy coordinates exclusively the adenine nucleobases present in the loop of the G-quadruplex. This exclusive single-site platination reflects the interaction of the compound with both the G-tetrad and the loop residues. In addition Pt-ttpy showed promising antiproliferative activity on a panel of cancer cell lines in a parallel study using cisplatin derivatives currently in clinical use.
authors: Institut Curie, Section Recherche, CNRS UMR176, Centre Universitaire Paris XI, Bât. 110, 91405, Orsay, France.
authors: Hélène
authors: H
authors: Bertrand
authors: Sophie
authors: S
authors: Bombard
authors: David
authors: D
authors: Monchaud
authors: Eric
authors: E
authors: Talbot
authors: Aurore
authors: A
authors: Guédin
authors: Jean-Louis
authors: JL
authors: Mergny
authors: Renate
authors: R
authors: Grünert
authors: Patrick J
authors: PJ
authors: Bednarski
authors: Marie-Paule
authors: MP
authors: Teulade-Fichou
mesh_terms: D000225:Adenine / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology; D013379:Substrate Specificity; D016615:Telomere / Q000737:chemistry* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010984:Platinum; D000225:Adenine