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Structural studies on acridine derivatives binding to telomeric DNA

Miles, S., Callow, P., Teixeira, S., Gan, Y., Denny, W., Cardin, C. and Forsyth, T. (2005) Structural studies on acridine derivatives binding to telomeric DNA. Physica B-Condensed Matter, 385-86 (2). pp. 845-847. ISSN 0921-4526

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To link to this item DOI: 10.1016/j.physb.2006.05.122

Abstract/Summary

Acridine derivatives can inhibit a variety of nuclear enzymes by binding or intercalating to DNA. This class of compounds is of great interest in the development of novel anticancer agents. Despite the availability of crystallographic data for some of the compounds complexed with DNA, uncertainties remain about the mechanisms of action, binding preferences and biological targets. To investigate the intercalation of several acridine derivatives, a variety of techniques are being employed. Single-crystal X-ray diffraction is being used to determine the high resolution three-dimensional structure of short sequences of quadruplex telomeric DNA with bound drug. This will be compared to the effect of drug binding to long segments of double-stranded DNA using fibre diffraction, with neutron diffraction studies planned to analyse the hydrogen bonding patterns of the DNA-drug complexes. Small-angle neutron scattering (SANS) will also be applied to study drug binding to both short and long sequences of quadruplex and double-stranded DNA in solution. Initial SANS measurements of the telomeric repeat d(TGGGGT) imply that this hexamer is present as a quadruplex. (c) 2006 Elsevier B.V. All rights reserved.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
ID Code:11481
Uncontrolled Keywords:SANS, DNA-drug complexes, X-ray crystallography, X-ray fibre diffraction
Additional Information:8th International Conference on Neutron Scattering Sydney, AUSTRALIA 27 NOV-2 DEC 2005

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