Conformations of complexes between mitomycin and decanucleotides. 2. Application of the model to mitomycin C derivatives. Extension to covalent binding with adenine

Abstract
Molecular mechanics simulation of the interactions of important mitomycin C analogues monocovalently bound to DNA models are presented. These analogues included substituents such as p-hydroxyphenyl, 2-mercaptoethyl, and dimethylamidinium on N7 of mitomycin C and the DNA models consisted of d(GCGCGCGCGC)2 and d(GCGCATGCGC)2. The excellent fits and strong binding affinities of these highly potent analogues support the usefulness of the model. The binding of a mitomycin-related N-phenylpyrrole with a carbamoyloxy substituent to O6 of guanine was studied. Finally, a reactive mitomycin intermediate proposed by Moore was shown to interact with DNA in a way consistent with the formation of a covalent adduct.