A platinum-quinacridine hybrid as a G-quadruplex ligand.
A novel platinum-quinacridine hybrid, comprising a monofunctional Pt moiety and a G-quadruplex ligand (mono-para-quinacridine or MPQ), has been synthesized and shown to interact with quadruplex DNA via a dual noncovalent/covalent binding mode. Denaturing gel electrophoresis was used to separate the various platination products of 22AG (an oligonucleotide that mimics the human telomeric repeat) by Pt-MPQ, and it was shown that two platinated adducts are highly stable quadruplex structures. Dimethylsulfate/piperidine treatment and 3'-exonuclease digestion of the isolated adducts allowed us to precisely determine the platination pattern of 22AG by Pt-MPQ, which displays three main sites G2, G10 and G22. Data presented herein support the hypothesis that Pt-MPQ traps preferentially the antiparallel structure of the 22AG quadruplex. Finally, the kinetics of Pt-MPQ platination using a construct containing both quadruplex DNA and a duplex DNA parts provide the first insights into the Pt-MPQ preference for quadruplex DNA over duplex DNA.
Bertrand
Hélène
H
Institut Curie, Section Recherche, CNRS UMR176, Centre Universitaire Paris XI, Bat. 110, 91405 Orsay, France.
Bombard
Sophie
S
Monchaud
David
D
Teulade-Fichou
Marie-Paule
MP
D000166:Acridines / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*
D000166:Acridines; D008024:Ligands; D009944:Organoplatinum Compounds; C524648:platinum-mono-para-quinacridine; D010984:Platinum; D006147:Guanine