A platinum-quinacridine hybrid as a G-quadruplex ligand

被引：83

作者：

Bertrand, Helene

Bombard, Sophie

Monchaud, David

Teulade-Fichou, Marie-Paule

机构：

[1] Univ Paris 05, CNRS UMR 8601, Chim & Biochim Pharmacol & Toxicol Lab, F-75006 Paris, France

[2] Ctr Univ Paris 11, CNRS UMR 176, Sect Rech, Inst Curie, F-91405 Orsay, France

来源：

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | 2007年 / 12卷 / 07期

关键词：

platinum; quinacridine; hybrid agent; G-quadruplex DNA;

D O I：

10.1007/s00775-007-0273-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1003 / 1014

页数：12

共 59 条

[1] Structure-activity relationships in platinum-acridinylthiourea conjugates: effect of the thiourea nonleaving group on drug stability, nucleobase affinity, and in vitro cytotoxicity [J].