title: Design of a G.C-specific DNA minor groove-binding peptide.
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.
authors.affiliation: Graduate Group in Biophysics, University of California, Berkeley 94720.
authors.forename: B H
authors.initials: BH
authors.lastname: Geierstanger
authors.forename: M
authors.initials: M
authors.lastname: Mrksich
authors.forename: P B
authors.initials: PB
authors.lastname: Dervan
authors.forename: D E
authors.initials: DE
authors.lastname: Wemmer
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D003196:Computer Graphics; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: C089983:ImPImP; D007093:Imidazoles; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D011758:Pyrroles; D004247:DNA