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Recognition of Base Mismatches in DNA by 5,6-Chrysenequinone Diimine Complexes of Rhodium(III): A Proposed Mechanism for Preferential Binding in Destabilized Regions of the Double Helix

Jackson, Brian A. and Barton, Jacqueline K. (2000) Recognition of Base Mismatches in DNA by 5,6-Chrysenequinone Diimine Complexes of Rhodium(III): A Proposed Mechanism for Preferential Binding in Destabilized Regions of the Double Helix. Biochemistry, 39 (20). pp. 6176-6182. ISSN 0006-2960. doi:10.1021/bi9927033. https://resolver.caltech.edu/CaltechAUTHORS:20160209-144358626

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Abstract

5,6-Chrysenequinone diimine (chrysi) complexes of rhodium(III) have been shown to be versatile and specific recognition agents for mismatched base pairs in DNA. The design of these compounds was based on the hypothesis that the sterically expansive chrysi ligand, which should be too wide to readily intercalate into B-DNA, would bind preferentially in the destabilized regions of the DNA helix near base mismatches. In this work, this recognition hypothesis is comprehensively explored. Comparison of the recognition patterns of the complex [Rh(bpy)_2(chrysi)]^(3+) with a nonsterically demanding analogue, [Rh(bpy)_2(phi)]^(3+) (phi = 9,10-phenanthrenequinone diimine), demonstrates that the chrysi ligand does indeed disfavor binding to B-DNA and generate mismatch selectivity. Examination of mismatch recognition by [Rh(bpy)_2(chrysi)]^(3+) in both constant and variable sequence contexts using photocleavage assays indicates that the recognition of base mismatches is influenced by the amount that a mismatch thermodynamically destabilizes the DNA helix. Thermodynamic binding constants for the rhodium complex at a range of mismatch sites have been determined by quantitative photocleavage titration and yield values which vary from 1 × 10^6 to 20 × 10^6 M^(-1). These mismatch-specific binding affinities correlate with independent measurements of thermodynamic destabilization, supporting the hypothesis that helix destabilization is a factor determining the binding affinity of the metal complex for the mismatched site. Although not the only factor involved in the binding of [Rh(bpy)_2(chrysi)]^(3+) to mismatch sites, a model is proposed where helix destabilization acts as the “door” which permits access of the sterically demanding intercalator to the base stack.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/bi9927033DOIArticle
http://pubs.acs.org/doi/abs/10.1021/bi9927033PublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/bi9927033PublisherSupporting Information
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2000 American Chemical Society. Received November 24, 1999; Revised Manuscript Received March 16, 2000. Publication Date (Web): April 26, 2000. B.A.J. acknowledges the NSF and the Parsons Foundation for predoctoral fellowships. We gratefully acknowledge the financial support of the National Institutes of Health (GM33309). We also thank the Parsons Foundation for fellowship support to B.A.J.
Funders:
Funding AgencyGrant Number
NSFUNSPECIFIED
Ralph M. Parsons FoundationUNSPECIFIED
NIHGM33309
Issue or Number:20
DOI:10.1021/bi9927033
Record Number:CaltechAUTHORS:20160209-144358626
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160209-144358626
Official Citation:Recognition of Base Mismatches in DNA by 5,6-Chrysenequinone Diimine Complexes of Rhodium(III):  A Proposed Mechanism for Preferential Binding in Destabilized Regions of the Double Helix Brian A. Jackson and Jacqueline K. Barton Biochemistry 2000 39 (20), 6176-6182 DOI: 10.1021/bi9927033
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64343
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Feb 2016 23:08
Last Modified:10 Nov 2021 23:29

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