title: Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin.
abstract: The designed peptide 1-methylimidazole-2-carboxamide netropsin (2-ImN) binds specifically to the sequence 5'-TGACT-3'. Direct evidence from NMR spectroscopy is presented that this synthetic ligand binds DNA as a 2:1 complex, which reveals that the structure is an antiparallel dimer in the minor groove of DNA. This is in contrast to the 1:1 complexes usually seen with most crescent-shaped minor groove binding molecules targeted toward A+T-rich tracts but reminiscent of a dimeric motif found for distamycin at high concentrations. These results suggest that sequence-dependent groove width may play an important role in allowing an expanded set of DNA binding motifs for synthetic peptides.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.
authors.forename: M
authors.initials: M
authors.lastname: Mrksich
authors.forename: W S
authors.initials: WS
authors.lastname: Wade
authors.forename: T J
authors.initials: TJ
authors.lastname: Dwyer
authors.forename: B H
authors.initials: BH
authors.lastname: Geierstanger
authors.forename: D E
authors.initials: DE
authors.lastname: Wemmer
authors.forename: P B
authors.initials: PB
authors.lastname: Dervan
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009429:Netropsin / Q000031:analogs & derivatives* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D008024:Ligands; D009838:Oligodeoxyribonucleotides; C076037:1-methylimidazole-2-carboxamide netropsin; D009429:Netropsin; D004247:DNA