title: Structural and dynamic characterization of the heterodimeric and homodimeric complexes of distamycin and 1-methylimidazole-2-carboxamide-netropsin bound to the minor groove of DNA.
abstract: NMR spectroscopy combined with molecular modeling was used to characterize a heterodimeric complex with Dst and 2-ImN bound in the minor groove of d(GCCTAACAAGG).d(CCTTGTTAGGC) (1:1:1 2-ImN.Dst.DNA complex). The imidazole-pyrrole-pyrrole ligand 2-ImN spans 5'-GTTA-3' of the TAACA.TGTTA binding site with the imidazole nitrogen specifically recognizing the guanine amino group. The Dst ligand lies along the 5'-AACA-3' sequence and complements the 2-ImN ligand in the formation of the antiparallel side-by-side heterodimeric complex. Titrations of the same site with Dst or 2-ImN alone yield homodimeric complexes (2:1 ligand.DNA) of lower stability than the 1:1:1 2-ImN.Dst.DNA complex. Dst and 2-ImN binding to d(CGCAAACTGGC).d(GCCAGTTTGCG) was also investigated. The 1:1:1 2-ImN.Dst.DNA complex is again the most stable complex with the AAACT.AGTTT site and is similar to the TAACA.TGTTA complex. No monomeric binding of either 2-ImN or Dst was observed to either site.
authors.affiliation: Graduate Group in Biophysics, University of California, Berkeley 94720.
authors.forename: B H
authors.initials: BH
authors.lastname: Geierstanger
authors.forename: J P
authors.initials: JP
authors.lastname: Jacobsen
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: D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004214:Distamycins; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009429:Netropsin / Q000031:analogs & derivatives*; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004214:Distamycins; D009838:Oligodeoxyribonucleotides; C076037:1-methylimidazole-2-carboxamide netropsin; D009429:Netropsin; D004247:DNA