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Sequence-Specific DNA Binding by a Rhodium Complex: Recognition Based on Sequence-Dependent Twistability

Terbrueggen, Robert H. and Barton, Jacqueline K. (1995) Sequence-Specific DNA Binding by a Rhodium Complex: Recognition Based on Sequence-Dependent Twistability. Biochemistry, 34 (26). pp. 8227-8234. ISSN 0006-2960. doi:10.1021/bi00026a003. https://resolver.caltech.edu/CaltechAUTHORS:20160405-140026640

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Abstract

The chemical construction of small molecules targeted to DNA depends upon the sequence dependent structure of the double helix. Here we describe a new structural element to be considered in the sequence-specific recognition of DNA, sequence-dependent DNA twistability. The importance of sequence-dependent DNA twistability is demonstrated in the DNA recognition properties of a novel synthetic rhodium intercalator, A-1-Rh(MGP)_2phi^(5+). This metallointercalator, containing pendant guanidinium groups, binds in the major groove of DNA at subnanomolar concentrations to the 6 base pair sequence 5'-CAT A TG-3' with enantiospecificity. An essential feature of this recognition is the sequence-specific unwinding of the DNA helix, which permits direct contacts between guanidinium functionalities on the metal complex and guanine residues. Through an assay developed to test for sequence-specific DNA unwinding, a 70 ± 10° unwinding of the sequence 5'-CATATG-3' is established with specific binding by the metal complex. This sequence-dependent twistability may be an essential feature of the recognition of sequences by DNA-binding proteins and may be exploited in future design.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/bi00026a003DOIArticle
http://pubs.acs.org/doi/abs/10.1021/bi00026a003PublisherArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 1995 American Chemical Society. Received March 22, 1995. Publication Date: July 1995. This work has been supported by the NIH (GM33309), which we gratefully acknowledge.
Funders:
Funding AgencyGrant Number
NIHGM33309
Issue or Number:26
DOI:10.1021/bi00026a003
Record Number:CaltechAUTHORS:20160405-140026640
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160405-140026640
Official Citation:Sequence-Specific DNA Binding by a Rhodium Complex: Recognition Based on Sequence-Dependent Twistability Robert H. Terbrueggen and Jacqueline K. Barton Biochemistry 1995 34 (26), 8227-8234 DOI: 10.1021/bi00026a003
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65941
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:06 Apr 2016 18:24
Last Modified:10 Nov 2021 23:51

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