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 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.
Zeglis
Brian M
BM
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Boland
Jennifer A
JA
Barton
Jacqueline K
JK
D020137:Base Pair Mismatch; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000528:radiation effects; D053837:DNA Cleavage; D009154:Mutation; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry* / Q000235:genetics / Q000528:radiation effects; D009942:Organometallic Compounds / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry*
D009711:Nucleotides; D009942:Organometallic Compounds; D004247:DNA; D012238:Rhodium