A platinum-quinacridine hybrid as a G-quadruplex ligand

J Biol Inorg Chem. 2007 Sep;12(7):1003-14. doi: 10.1007/s00775-007-0273-3. Epub 2007 Jul 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemistry*
  • Electrophoresis, Agar Gel
  • G-Quadruplexes
  • Guanine / chemistry*
  • Ligands
  • Molecular Structure
  • Organoplatinum Compounds / chemistry*
  • Platinum / chemistry*

Substances

  • Acridines
  • Ligands
  • Organoplatinum Compounds
  • platinum-mono-para-quinacridine
  • Platinum
  • Guanine