title: Molecular mechanics simulations on covalent complexes of mitomycin C and its analogues with left-handed DNA duplexes.
abstract: We present molecular mechanics simulations on covalent complexes between d(GCGCGCGCGC).d(GCGCGCGCGC) in the left-handed double helical forms (B and Z) and potent antitumor antibiotics mitomycin C and three of its analogues using the all atom force field in the framework of the program AMBER(UCSF). The energy-refined models of the complexes show interesting networks of hydrogen-bonding interactions between the drugs and DNA groups in the minor groove of the left-handed helices. The energy-refined models suggest that mitomycins could bind strongly to left-handed helices. This result might be relevant to the interpretation of earlier experiments which suggested that DNA bound by mitomycin C underwent a transition to a non-Z left-handed structure.
authors.affiliation: Searle Research and Development, Division of G.D. Searle and Company, Skokie, Illinois 60077.
authors.forename: S N
authors.initials: SN
authors.lastname: Rao
authors.forename: B S
authors.initials: BS
authors.lastname: Iyengar
authors.forename: T P
authors.initials: TP
authors.lastname: Wunz
authors.forename: W A
authors.initials: WA
authors.lastname: Remers
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D016685:Mitomycin / Q000378:metabolism*; D008937:Mitomycins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
chemical_list: D008937:Mitomycins; D016685:Mitomycin; D004247:DNA