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Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2 carboxamide netropsin

Mrksich, Milan and Wade, Warren S. and Dwyer, Tammy J. and Geierstanger, Bernhard H. and Wemmer, David E. and Dervan, Peter B. (1992) Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2 carboxamide netropsin. Proceedings of the National Academy of Sciences of the United States of America, 89 (16). pp. 7586-7590. ISSN 0027-8424. PMCID PMC49755. http://resolver.caltech.edu/CaltechAUTHORS:MRKpnas92

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Abstract

The designed peptide 1-methylimidazole-2-carboxamide netropsin (2-ImN) binds specifically to the sequence 5'-TGACT-3'. Direct evidence from NMR spectroscopy is presented that this synthetic ligand binds DNA as a 2:1 complex, which reveals that the structure is an antiparallel dimer in the minor groove of DNA. This is in contrast to the 1:1 complexes usually seen with most crescent-shaped minor groove binding molecules targeted toward A+T-rich tracts but reminiscent of a dimeric motif found for distamycin at high concentrations. These results suggest that sequence-dependent groove width may play an important role in allowing an expanded set of DNA binding motifs for synthetic peptides.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC49755/PubMed CentralArticle
http://dx.doi.org/10.1073/pnas.89.16.7586DOIArticle
Additional Information:© 1992 by the National Academy of Sciences. Contributed by Peter B. Dervan, May 6, 1992. We are grateful to the National Institutes of Health (GM-27681 to P.B.D. and GM-43129 to D.E.W.) and Burroughs Wellcome for research support, a National Science Foundation predoctoral fellowship to W.S.W., a National Institutes of Health Research Service Award to M.M., and instrument grants from the U.S. Department of Energy (DE FG05-86ER75281) and the National Science Foundation (DMB 86-09305 and BBS 87-20134). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
NIHGM-27681
NIHGM-43129
Burroughs WellcomeUNSPECIFIED
NSF Predoctoral FellowshipUNSPECIFIED
NIH Predoctoral FellowshipUNSPECIFIED
Department of Energy (DOE)DE-FG05-86ER75281
NSFDMB 86-09305
NSFBBS 87-20134
Subject Keywords:N-METHYLPYRROLECARBOXAMIDE; MOLECULAR RECOGNITION; NUCLEIC-ACIDS; DISTAMYCIN-A; BASE-PAIRS; BINDING; COMPLEX; NMR; OLIGOPEPTIDES; DODECAMER
PubMed Central ID:PMC49755
Record Number:CaltechAUTHORS:MRKpnas92
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:MRKpnas92
Alternative URL:http://www.pnas.org/cgi/content/abstract/89/16/7586
Official Citation:M Mrksich, W S Wade, T J Dwyer, B H Geierstanger, D E Wemmer, and P B Dervan Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin. PNAS 1992 89 (16) 7586-7590; doi:10.1073/pnas.89.16.7586
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1483
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Jan 2006
Last Modified:09 May 2016 18:39

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