Interactions of a new antitumor antibiotic BBM-928A with deoxyribonucleic acid. Bifunctional intercalative binding studied by fluorometry and viscometry

Abstract

A new actinoleukin-like antitumor antibiotic, BBM-928A, interacts with isolated DNA molecules. BBM-928A contains 2 substituted quinolines linked by a cyclic decapeptide. Quenching effects of the covalently closed superhelical [bacteriophage] PM2 DNA on the BBM-928A fluorescence revealed a strong interaction with an apparent association constant of 1.93 .times. 107 M-1 and with 11 DNA nucleotides per BBM-928A binding site. Viscometric studies indicated that BBM-928A induced an unwinding-rewinding process of the closed superhelical PM2 DNA typically observed for DNA intercalators. The unwinding angle (43.degree.) induced by BBM-928A was almost twice that of the ethidium bromide (26.degree.), a monofunctional intercalator. The BBM-928A-induced increase of the helix length of sonicated rodlike calf thymus DNA was .apprx. 1.5-fold that induced by the ethidium bromide. BBM-928A apparently bifunctionally intercalated with DNA in a manner similar to the bifunctional intercalation of echinomycin.