Targeting Abasic Sites and Single Base Bulges in DNA with Metalloinsertors

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) × 10^6 M^(−1)), comparably to the metalloinsertor and a CC mismatch. The complex binds single base bulge sites with lower affinity (∼10^5 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.

Files

Additional details