Synthesis and DNA binding of [3-[2'-(2-acetamidoethyl)-2,4'-bithiazole-4-carboxamido]propyl]dimethylsulfonium chloride, a fragment of bleomycin A2

Abstract

[3-[2''-(2-Acetamidoethyl)-2,4''-bithiazole-4-carboxamido]propyl]dimethylsulfonium chloride, the acetyl derivative of the cationic terminal dipeptide of [the antineoplastic drug] bleomycin A2, was synthesized. Its binding to [calf thymus] DNA and poly(dA-dT) was studied by 1H-NMR and fluorescence spectroscopy. The spectral perturbations which occur upon binding of the compound to either nucleic acid indicate that that portion of bleomycin which binds to the nucleic acid can, for the most part, be mimicked by the fragment. The data are discussed in terms of the structure of the drug and the drug-nucleic acid complex.