Targeting abasic sites and single base bulges in DNA with metalloinsertors |
| |
Authors: | Zeglis Brian M Boland Jennifer A Barton Jacqueline K |
| |
Institution: | Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|