Work

Targeting Abasic Sites and Single Base Bulges in DNA with Metalloinsertors

Year: 2008

Type: article

Abstract: The site-specific recognition of abasic sites and single base bulges in duplex DNA by sterically expansive rhodium metalloinsertors has been investigated. Through DNA photocleavage experiments, Rh(bpy)2(chrysi)3+ is shown to bind both abasic sites and single base bulges site-specifically and, upon irradiation, to cleave the backbone of the defect-containing DNA. Photocleavage titrations reveal that the metal complex binds DNA containing an abasic site with high affinity (2.6(5) x 106 M-1), comparably to the metalloinsertor and a CC mismatch. The complex binds single base bulge sites with lower affinity (approximately 105 M-1). Analysis of cleavage products and the correlation of affinities with helix destabilization suggest that Rh(bpy)2(chrysi)3+ binds both lesions via metalloinsertion, as observed for Rh binding at mismatched sites, a binding mode in which the mismatched or unpaired bases are extruded from the helix and replaced in the base stack by the sterically expansive ligand of the metalloinsertor.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja801479y

Authors: Brian M. Zeglis, Jennifer A. Boland, Jacqueline K. Barton

Institution: California Institute of Technology

Language: English

Topic: Metal complexes synthesis and properties

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: G4373289177, G7548229278, METAL PROBES AND DRUG BINDING TO DNA