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

Moorhouse, A. D., Haider, S., Gunaratnam, M., Munnur, D., Neidle, S., Moses, J. E. (June 2008) Targeting telomerase and telomeres: a click chemistry approach towards highly selective G-quadruplex ligands. Mol Biosyst, 4 (6). pp. 629-42. ISSN 1742-2051

DOI: 10.1039/b801822g


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.

Item Type: Paper
Additional Information: Molecular bioSystems
Uncontrolled Keywords: Benzene Derivatives/chemical synthesis/chemistry/*pharmacology Binding Sites Computer Simulation DNA/*chemistry/*metabolism G-Quadruplexes/*drug effects Ligands Models, Chemical Models, Molecular Molecular Structure Stereoisomerism Structure-Activity Relationship Substrate Specificity Telomerase/*antagonists & inhibitors/metabolism Telomere/chemistry/*metabolism Triazoles/chemical synthesis/chemistry/*pharmacology
CSHL Authors:
Communities: CSHL labs > Moses lab
Depositing User: Matthew Dunn
Date: June 2008
Date Deposited: 19 Apr 2021 21:34
Last Modified: 19 Apr 2021 21:34
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