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Sequence-Selective DNA Recognition and Photocleavage: A Comparison of Enantiomers of Rh(en)_2phi^(3+)

Shields, Thomas P. and Barton, Jacqueline K. (1995) Sequence-Selective DNA Recognition and Photocleavage: A Comparison of Enantiomers of Rh(en)_2phi^(3+). Biochemistry, 34 (46). pp. 15037-15048. ISSN 0006-2960. doi:10.1021/bi00046a009. https://resolver.caltech.edu/CaltechAUTHORS:20160405-140026070

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Abstract

The recognition and photoinduced cleavage of DNA by the enantiomers of bis(ethy1enediamine)-(9,10-phenanthrenequinone diimine)Rh(III) [Rh(en)_2phi^(3+)] have been characterized and the basis for enantioselective differences delineated. Rh(en)_2phi^(3+) isomers bind strongly to DNA via intercalation and, upon photoactivation with near-UV light, produce direct strand cleavage. On the basis of product analysis, the photoinduced DNA cleavage appears to proceed by a mechanism consistent with that observed for the parent Rh(phen)_2phi^(3+), involving direct abstraction of the 3’-hydrogen atom of the deoxyribose by the activated, intercalated phi. Quantitative photocleavage titrations indicate tight binding by both enantiomers to the DNA duplex. For A-Rh(en)_2phi^(3+), DNA site affinities range from 0.3 x 10^6 to 8.0 x 10^6 M^(-l), and a distinct preference for GC sites is evident. A-Rh(en)_2phi^(3+) is found to be sequence neutral with an average site affinity of 2 x 10^6 M^(-1). The basis for sequence selectivity of the enantiomers has been examined through comparison of photocleavage patterns to those of several phi complexes of rhodium(III) containing or lacking axial amines; those complexes containing the axial amines are found to target GC sites. DNA photocleavage studies on oligonucleotides containing the modified bases O^6- methylguanine, 7-deazaguanine, and deoxyuracil have been utilized to determine points of interaction on the DNA helix. These results establish binding by both complexes in the major groove of DNA. Differences in site recognition between enantiomers are attributed to the different hydrogen bonding and van der Waals contacts available in the major groove for the ancillary ethylenediamine ligands which differ in disposition in the two isomers.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/bi00046a009DOIArticle
http://pubs.acs.org/doi/abs/10.1021/bi00046a009PublisherArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 1995 American Chemical Society. Received June 13, 1995; Revised Manuscript Received August 25, 1995. Publication Date: November 1995. Supported by grants to J.K.B. from the National Institutes of Health (GM33309) and an NIH-NRSA predoctoral fellowship to T.P.S.
Funders:
Funding AgencyGrant Number
NIHGM33309
NIH Predoctoral FellowshipUNSPECIFIED
Issue or Number:46
DOI:10.1021/bi00046a009
Record Number:CaltechAUTHORS:20160405-140026070
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160405-140026070
Official Citation:Sequence-Selective DNA Recognition and Photocleavage: A Comparison of Enantiomers of Rh(en)2phi3+ Thomas P. Shields and Jacqueline K. Barton Biochemistry 1995 34 (46), 15037-15048 DOI: 10.1021/bi00046a009
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65939
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:06 Apr 2016 18:37
Last Modified:10 Nov 2021 23:51

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