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) × 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.
© 2008 American Chemical Society. Received February 27, 2008. Publication Date (Web): May 21, 2008. We are grateful to the NIH (GM33309) for their financial support, the SURF program for a summer internship for J.A.B, and the NSF for a graduate fellowship to B.M.Z.
Accepted Version - nihms97864.pdf
Supplemental Material - ja801479y-file002.pdf