The antitumor agent mitoxantrone binds cooperatively to DNA: evidence for heterogeneity in DNA conformation.

摘要: The equilibrium binding of the antitumor compound DHAQ, or mitoxantrone [1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10- anthracenedione], to various DNAs has been examined by optical titration and dialysis methods. At low r (bound drug/DNA base pair) values, less than 0.03, DHAQ binds, in a highly cooperative manner, calf thymus Micrococcus lysodeikticus DNAs. isotherms for interaction with Clostridium perfringens DNA poly(dA-dT).poly(dA-dT) exhibit small positive slope at suggestive binding. In contrast, poly(dG-dC).poly(dG-dC) shows no evidence even very values. higher values (r greater 0.05), all studied is characterized neighbor-exclusion process. A model proposed account two modes exhibited isotherms. main feature that local sequence structural heterogeneity give rise sets sites which binds while majority bind via This two-site reproduces observed leads conclusion clusters selected regions DNA. It suggested clustering may play role physiological activity drugs.