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.
Geierstanger
B H
BH
Graduate Group in Biophysics, University of California, Berkeley 94720.
Mrksich
M
M
Dervan
P B
PB
Wemmer
D E
DE
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
C089983:ImPImP; D007093:Imidazoles; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D011758:Pyrroles; D004247:DNA