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.

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.