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 characte rize a heterodimeric complex with Dst and 2-ImN bound in the minor gro ove of d(GCCTAACAAGG).d(CCTTGTTAGGC) (1:1:1 2-ImN.Dst.DNA complex). Th e imidazole-pyrrole-pyrrole ligand 2-ImN spans 5'-GTTA-3' of the TAACA .TGTTA binding site with the imidazole nitrogen specifically recognizi ng the guanine amino group. The Dst ligand lies along the 5'-AACA-3' s equence and complements the 2-ImN ligand in the formation of the antip arallel side-by-side heterodimeric complex. Titrations of the same sit e 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-Im N 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 monomer ic binding of either 2-ImN or Dst was observed to either site.