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.
Additional Information
© 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.Attached Files
Accepted Version - nihms97864.pdf
Supplemental Material - ja801479y-file002.pdf
Files
Name | Size | Download all |
---|---|---|
md5:2ba22c5a7bc737d0b603e2ef16e4eef0
|
437.8 kB | Preview Download |
md5:e7e2af064220a4dceeb026b409bd937f
|
502.6 kB | Preview Download |
Additional details
- PMCID
- PMC2759749
- Eprint ID
- 64811
- DOI
- 10.1021/ja801479y
- Resolver ID
- CaltechAUTHORS:20160226-135927342
- NIH
- GM33309
- Caltech Summer Undergraduate Research Fellowship (SURF)
- NSF Graduate Research Fellowship
- Created
-
2016-02-29Created from EPrint's datestamp field
- Updated
-
2021-11-10Created from EPrint's last_modified field