Targeting telomerase and telomeres: a click chemistry approach towards highly selective G-quadruplex ligands.

A.D. Moorhouse, Shozeb Haider, M. Gunaratnam, D. Munnur, S. Neidle, J.E. Moses

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Maintenance of telomeres—specialized complexes that protect the ends of chromosomes, is undertaken by the enzyme complex telomerase, which is a key factor that is activated in more than 80% of cancer cells, but is absent in most normal cells. Targeting telomere maintenance mechanisms could potentially halt tumour growth across a broad spectrum of cancer types, with little cytotoxic effect outside cancer cells. Here, we describe in detail a new class of G-quadruplex binding ligands synthesized using a click chemistry approach. These ligands comprise a 1,3-di(1,2,3-triazol-4-yl)benzene pharmacophore, and display high levels of selectivity for interaction with G-quadruplex DNA vs. duplex DNA. The ability of these ligands to inhibit the enzymatic activity of telomerase correlates with their ability to stabilize quadruplex DNA, and with estimates of affinity calculated by molecular modeling.
Original languageEnglish
Pages (from-to)629-642
Number of pages14
JournalMolecular bioSystems
Volume4(6)
Issue number6
DOIs
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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