STRUCTURAL REQUIREMENTS FOR MITOMYCIN-C DNA BONDING

Information of the specific structure of the activated mitomycin speci es leading to selective DNA bonding has been secured by determining th e bonding sequence selectivities of modified mitomycins in which the i dentity, spatial orientation, and state of unsaturation of the C-9 and C-9a substituents in the mitomycin were varied. Both mitomycin-9a-sul fonate (8) and mitomycin D (9) gave DNA bonding profiles comparable to those obtained for mitomycin C (1) under reductive conditions, indica ting that neither the stereochemistry of the C-9 and C-9a substituents nor the identity of the leaving group at C-9a influenced the site(s) of DNA bonding. These results indicated that aromatization of the dihy dropyrrole ring in mitomycin C precedes DNA binding and mitomycin C-1 bonding.