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Design of a G•C-Specific DNA Minor Groove-Binding Peptide

Geierstanger, Bernhard H. and Mrksich, Milan and Dervan, Peter B. and Wemmer, David E. (1994) Design of a G•C-Specific DNA Minor Groove-Binding Peptide. Science, 266 (5185). pp. 646-650. ISSN 0036-8075.

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A four-ring tripeptide containing alternating imidazole and pyrrole carboxamides specifically binds six-base pair 5'-(A,T)GCGC(A,T)-3' sites in the minor groove of DNA. The designed peptide has a specificity completely reversed from that of the tripyrrole distamycin, which binds A,T sequences. Structural studies with nuclear magnetic resonance revealed that two peptides bound side-by-side and in an antiparallel orientation in the minor groove. Each of the four imidazoles in the 2:1 ligand-DNA complex recognized a specific guanine amino group in the GCGC core through a hydrogen bond. Targeting a designated four- base pair G•C tract by this synthetic ligand supports the generality of the 2:1 peptide-DNA motif for sequence-specific minor groove recognition of DNA.

Item Type:Article
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URLURL TypeDescription
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1994 American Association for the Advancement of Science. 6 July 1994; accepted 2 September 1994. We are grateful to NIH (grants GM-27681 to P.B.D. and GM-43129 to D.E.W.) and the National Foundation for Cancer Research for research support, to the Ralph M. Parsons Foundation for a graduate fellowship to M.M., and to the U.S. Department of Energy (DE FG05-86ER75281) and NSF (DMB 86-09305 and BBS 87-20134) for instrumentation grants. The authors especially thank T. J. Dwyer for her contributions to the project. B.H.G. and D.E.W. also thank J. P. Jacobsen, H. P. Spielmann, and P. A. Fagan for helpful discussions.
Funding AgencyGrant Number
Ralph M. Parsons FoundationUNSPECIFIED
Department of Energy (DOE)DE FG05-86ER75281
NSFDMB 86-09305
NSFBBS 87-20134
Issue or Number:5185
Record Number:CaltechAUTHORS:20150127-110614368
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Official Citation:Design of a G•C-Specific DNA Minor Groove-Binding Peptide Bernhard H. Geierstanger, Milan Mrksich, Peter B. Dervan and David E. Wemmer Science New Series, Vol. 266, No. 5185 (Oct. 28, 1994) , pp. 646-650 Published by: American Association for the Advancement of Science Stable URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:54140
Deposited By: Ruth Sustaita
Deposited On:27 Jan 2015 21:33
Last Modified:26 Nov 2019 11:15

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