title: Conformations of complexes between mitomycins and decanucleotides. 3. Sequence specificity, binding at C-10, and mitomycin analogues.
abstract: Molecular mechanics simulation of the interactions of mitomycin C and certain analogues with DNA models are presented. The sequence specificity of mitomycin C binding was investigated by using a d(GCGCGCGCGC)2 decanucleotide duplex, abbreviated herein as GC10, in which the base pair was varied on either side of the covalent binding site. A CGT fragment was favored, although its correlation with the diverse findings in the literature is questionable. A model was derived for the monocovalent binding at C10 of 2,7-diaminomitosene with GC10 and for the noncovalently bound hydroquinone intermediate. Revised models were established for three highly active mitomycin C analogues: M-83, BMY-25282, and RR-150. They involved covalent binding at the 2-amino group of a guanine residue, and they accounted for enhanced noncovalent binding afforded by specific interactions of the C7 substituents with residues in GC10.
authors.affiliation: Department of Pharmaceutical Sciences, University of Arizona, Tucson 85721.
authors.forename: W A
authors.initials: WA
authors.lastname: Remers
authors.forename: S N
authors.initials: SN
authors.lastname: Rao
authors.forename: T P
authors.initials: TP
authors.lastname: Wunz
authors.forename: P A
authors.initials: PA
authors.lastname: Kollman
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D007941:Leukemia P388 / Q000378:metabolism; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000138:chemical synthesis / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*
chemical_list: D008937:Mitomycins; D009838:Oligodeoxyribonucleotides; D016685:Mitomycin; C027281:7-N-(4-hydroxyphenyl)mitomycin C; C043641:7-cysteaminomitosane; C046941:N(6)-((dimethylamino)methylene)mitomycin C; D004247:DNA