Targeting abasic sites and single base bulges in DNA with metalloinsertors

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 10(6) M-1), comparably to the metalloinsertor and a CC mismatch. The complex binds single base bulge sites with lower affinity (similar to 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 metalloinserter.