Crystallographic studies of quadruplex nucleic acids

Campbell, N.H. and Parkinson, G.N. (2007) Crystallographic studies of quadruplex nucleic acids. Methods, 43 (4). pp. 252-263. 10.1016/j.ymeth.2007.08.005.

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DOI: 10.1016/j.ymeth.2007.08.005

Abstract

DNA quadruplexes are formed from guanine-rich repeats that self-associate into higher order four-stranded structures. These G-rich repeat sequences can be found in both telomeric regions as well as regions proximal to promoters of oncogenes. The compelling evidence that stabilizing these motifs by small molecule ligands can alter cell viability in certain cancer cell lines has led to identification of DNA quadruplex structures as therapeutic targets. Target-based design of selective ligands that target particular quadruplex topologies is heavily reliant on the availability of high-resolution structural information of the intended target. X-ray crystallography can provide this level of detail to atomic resolution. Recently drug discovery programs have refocused on the need for a fuller structural and molecular description of the target molecule. This review describes a crystallographic route to the determination of quadruplex topology, and high-resolution loop structures for target-based ligand design. The review also highlights the methods employed in the design of appropriate DNA sequences and crystallization techniques to solve these unusual DNA structures.

Item Type:Article
Uncontrolled Keywords:Quadruplex; Crystallization; Structure solution; Structure determination; X-ray crystallography; Nucleic acids
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2416
Journal or Publication Title:Methods
Deposited By:Library Staff
Deposited On:04 Nov 2011 17:06
Last Modified:04 Nov 2011 17:24

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