Published October 28, 1994 | Version public
Journal Article

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

  • 1. ROR icon University of California, Berkeley
  • 2. ROR icon California Institute of Technology

Abstract

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.

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.

Additional details

Identifiers

Eprint ID
54140
Resolver ID
CaltechAUTHORS:20150127-110614368

Related works

Funding

NIH
GM-27681
NIH
GM-43129
Ralph M. Parsons Foundation
Department of Energy (DOE)
DE FG05-86ER75281
NSF
DMB 86-09305
NSF
BBS 87-20134

Dates

Created
2015-01-27
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Updated
2021-11-10
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