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Design of a Covalent Peptide Heterodimer for Sequence-Specific Recognition in the Minor Groove of Double-Helical DNA

Mrksich, Milan and Dervan, Peter B. (1994) Design of a Covalent Peptide Heterodimer for Sequence-Specific Recognition in the Minor Groove of Double-Helical DNA. Journal of the American Chemical Society, 116 (8). pp. 3663-3664. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20160510-133138018

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Abstract

While 1:1 peptide-DNA models aided in the design of oligopeptides for recognition of long tracts of contiguous A,T base pairs of DNA, early efforts to design peptides for recognition of mixed A,T and G,C sequences met with limited success. The synthetic peptides 2-PyN and2-ImN, targeted to the 5'-TGTTA- 3' site as 1:1 complexes, were found to bind the unanticipated sequence 5'-TGTCA-3' as anti parallel side-by-side dimers in the minor groove. These and other recent 2:1 peptide-DNA complexes offer a revised model for the design of ligands for sequence-specific recognition in the minor groove of DNA. In addition to sequence-dependent minor groove width being a determinant of specificity, the 2:1 model allows specific contacts with each strand on the floor of the minor groove. Based on this new understanding, we report here a successful second generation molecule, a covalent peptide heterodimer, which specifically binds the designated sequence 5'-TGTTA-3'.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja00087a088DOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja00087a088PublisherArticle
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1994 American Chemical Society. Received January 12, 1994. We are grateful to the National Institutes of Health (GM-27681) for research support and the Ralph M. Parsons Foundation for a Graduate Fellowship to M.M.
Funders:
Funding AgencyGrant Number
NIHGM-27681
Ralph M. Parsons FoundationUNSPECIFIED
Issue or Number:8
Record Number:CaltechAUTHORS:20160510-133138018
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-133138018
Official Citation:Design of a Covalent Peptide Heterodimer for Sequence-Specific Recognition in the Minor Groove of Double-Helical DNA Milan Mrksich and Peter B. Dervan Journal of the American Chemical Society 1994 116 (8), 3663-3664 DOI: 10.1021/ja00087a088
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66911
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:19 May 2016 16:47
Last Modified:26 Nov 2019 11:15

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