Exclusive platination of loop adenines in the human telomeric G-quadruplex

Org Biomol Chem. 2009 Jul 21;7(14):2864-71. doi: 10.1039/b904599f. Epub 2009 Jun 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / chemistry*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Circular Dichroism
  • G-Quadruplexes*
  • Humans
  • Models, Molecular
  • Nucleic Acid Conformation
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology
  • Platinum / chemistry*
  • Platinum / pharmacology
  • Substrate Specificity
  • Telomere / chemistry*
  • Telomere / genetics

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Platinum
  • Adenine