The extreme 3′-ends of human telomeres consist of 150–250 nucleotides of single-stranded DNA sequence together with associated proteins. Small-molecule ligands can compete with these proteins and induce a conformational change in the DNA to a four-stranded quadruplex arrangement, which is also no longer a substrate for the telomerase enzyme. The modified telomere ends provide signals to the DNA-damage-response system and trigger senescence and apoptosis. Experimental structural data are available on such quadruplex complexes comprising up to four telomeric DNA repeats, but not on longer systems that are more directly relevant to the single-stranded overhang in human cells. The present paper reports on a molecular modelling study that uses Molecular Dynamics simulation methods to build dimer and tetramer quadruplex repeats. These incorporate ligand-binding sites and are models for overhang–ligand complexes.
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June 2009
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Conference Article|
May 20 2009
A molecular model for drug binding to tandem repeats of telomeric G-quadruplexes
Shozeb M. Haider;
Shozeb M. Haider
1CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29–39 Brunswick Square, London, WC1N 1AX, U.K.
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Stephen Neidle
Stephen Neidle
1
1CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29–39 Brunswick Square, London, WC1N 1AX, U.K.
1To whom correspondence should be addressed (email stephen.neidle@pharmacy.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 02 2009
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem Soc Trans (2009) 37 (3): 583–588.
Article history
Received:
March 02 2009
Citation
Shozeb M. Haider, Stephen Neidle; A molecular model for drug binding to tandem repeats of telomeric G-quadruplexes. Biochem Soc Trans 1 June 2009; 37 (3): 583–588. doi: https://doi.org/10.1042/BST0370583
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