Design of Peptides That Bind in the Minor Groove of DNA at 5′-(A,T)G(A,T)C(A,T)-3′ Sequences by a Dimeric Side-by-Side Motif

Warren S. Wade, Milan Mrksich, Peter B. Dervan*

*Corresponding author for this work

Research output: Contribution to journalArticle

247 Scopus citations

Abstract

The designed peptides pyridine-2-carboxamide-netropsin (2-PyN) and 1-methylimidazole-2-carboxamide-netropsin (2-ImN) are crescent-shaped synthetic analogs of the natural products netropsin (N) and distamycin A (D). Footprinting experiments indicate that the peptides 2-PyN and 2-ImN bind specifically the 5 base pair sequence 5′-TGTCA-3′. Affinity cleaving data suggest that the complexes, 2-ImN.5′-TGTCA-3′ and 2-PyN.5′-TGTCA-3′, are composed of two equivalent orientations which disfavor a 1:1 model. The footprinting and affinity cleaving data are in accord with a 2:1 complex where a novel side-by-side antiparallel dimer binds in the minor groove of double-helical DNA.

Original languageEnglish (US)
Pages (from-to)8783-8794
Number of pages12
JournalJournal of the American Chemical Society
Volume114
Issue number23
DOIs
StatePublished - Nov 1 1992

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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