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

Bernhard H. Geierstanger, Milan Mrksich, Peter B. Dervan*, David E. Wemmer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

212 Scopus citations

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 distal mycin, 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.

Original languageEnglish (US)
Pages (from-to)646-650
Number of pages5
JournalScience
Volume266
Issue number5185
DOIs
StatePublished - 1994

ASJC Scopus subject areas

  • General

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