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DNA Strand Cleavage near a CC Mismatch Directed by a Metalloinsertor

Lim, Mi Hee and Lau, Irvin H. and Barton, Jacqueline K. (2007) DNA Strand Cleavage near a CC Mismatch Directed by a Metalloinsertor. Inorganic Chemistry, 46 (23). pp. 9528-9530. ISSN 0020-1669. PMCID PMC2747586. doi:10.1021/ic701598k. https://resolver.caltech.edu/CaltechAUTHORS:20160302-071129473

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Abstract

Reagents for recognition and efficient cleavage of mismatched DNA without photoactivation were designed. They contain a combination of a mismatch-directing metalloinsertor, [Rh(bpy)_2(chrysi)]^(3+) (bpy = 2,2‘-bipyridyl, chrysi = 5,6-chrysenequinone diimine), and an oxidative cleavage functionality, [Cu(phen)_2]^+ (Cu). Both unconjugated (Rh+Cu) and conjugated (Rh−Cu) frameworks of the Rh insertor and Cu were prepared. Compared to Cu, both constructs Rh+Cu and Rh−Cu exhibit efficient site-specific DNA scission only with mismatched DNA, confirmed by experiments with ^(32)P-labeled oligonucleotides. Furthermore, these studies indicate that DNA cleavage occurs near the mismatch in the minor groove and on both strands. Interestingly, the order of reactivity of the three systems with a CC mismatch is Rh+Cu > Rh−Cu ≫ Cu. Rh binding appears to direct Cu reactivity with or without tethering. These results illustrate advantages and disadvantages in bifunctional conjugation.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ic701598kDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ic701598kPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ic701598kPublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747586/PubMed CentralArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2007 American Chemical Society. Received August 10, 2007. Publication Date (Web): October 6, 2007. We are grateful to the NIH (Grant GM33309) and Applied Biosystems for their financial support. We also thank the Tobacco-Related Disease Research Program (TRDRP) for a postdoctoral fellowship to M.H.L.
Funders:
Funding AgencyGrant Number
NIHGM33309
Applied BiosystemsUNSPECIFIED
California Tobacco-Related Disease Research Program (TRDRP)UNSPECIFIED
Issue or Number:23
PubMed Central ID:PMC2747586
DOI:10.1021/ic701598k
Record Number:CaltechAUTHORS:20160302-071129473
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160302-071129473
Official Citation:DNA Strand Cleavage near a CC Mismatch Directed by a Metalloinsertor Mi Hee Lim, Irvin H. Lau, and Jacqueline K. Barton Inorganic Chemistry 2007 46 (23), 9528-9530 DOI: 10.1021/ic701598k
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64941
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:02 Mar 2016 18:16
Last Modified:10 Nov 2021 23:37

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