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Science 28 October 1994:
Vol. 266. no. 5185, pp. 646 - 650
DOI: 10.1126/science.7939719
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Articles

Science, Vol 266, Issue 5185, 646-650
Copyright © 1994 by American Association for the Advancement of Science

articles

Design of a G.C-specific DNA minor groove-binding peptide

BH Geierstanger, M Mrksich, PB Dervan, and DE Wemmer

Graduate Group in Biophysics, University of California, Berkeley 94720.

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.


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