Design and binding of a distamycin A analog to d(CGCAAGTTGGC).cntdot.d(GCCAACTTGCG): synthesis, NMR studies, and implications for the design of sequence-specific minor groove binding oligopeptides

An oligopeptide has been synthesized in which an imidazole ring is substituted for the central pyrrole ring of distamycin A. Two-dimensional NMR spectroscopy was used to characterize the complex formed between 3-[1-methyl-4-[1-methyl-4-[1-methyl-4-(formylamino)pyrrole-2-carboxamido]imidazole-2-carboxamido]pyrrole-2-carboxamido]propionamidine hydrochloride (2-ImD) and d(CGCAAGTTGGC).d(GCCAACTTGCG). Titration of the AAGTT duplex with 2-ImD yielded a single complex with a ligand:DNA stoichiometry of 2:1