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. doi:10.1073/pnas.89.16.7586. https://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.
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| 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. | ||||||||||||||||||
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| Subject Keywords: | N-METHYLPYRROLECARBOXAMIDE; MOLECULAR RECOGNITION; NUCLEIC-ACIDS; DISTAMYCIN-A; BASE-PAIRS; BINDING; COMPLEX; NMR; OLIGOPEPTIDES; DODECAMER | ||||||||||||||||||
| Issue or Number: | 16 | ||||||||||||||||||
| PubMed Central ID: | PMC49755 | ||||||||||||||||||
| DOI: | 10.1073/pnas.89.16.7586 | ||||||||||||||||||
| Record Number: | CaltechAUTHORS:MRKpnas92 | ||||||||||||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:MRKpnas92 | ||||||||||||||||||
| 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: | 08 Nov 2021 19:10 |
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