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