Interactions of a new antitumor antibiotic BBM-928A with deoxyribonucleic acid. Bifunctional intercalative binding studied by fluorometry and viscometry.
A new actinoleukin-like antitumor antibiotic, BBM-928A, has been shown to interact with isolated DNA molecules. BBM-928A contains two substituted quinolines linked by a cyclic decapeptide. Quenching effects of the covalently closed superhelical PM2 DNA on the BBM-928A fluorescence revealed a strong interaction with an apparent association constant of 1.93 x 10(7) M-1 and with 11 deoxyribonucleic acid (DNA) nucleotides per BBM-928A binding site. Viscometric studies indicated the BBM-928A induced an unwinding-rewinding process of the closed superhelical PM2 DNA typically observed for DNA intercalators. The unwinding angle (43 degrees) induced by BBM-928A was almost twice that of the ethidium bromide (26 degrees), a monofunctional intercalator. The BBM-928A-induced increase of the helix length of sonicated rodlike calf thymus DNA was approximately 1.5-fold that induced by the ethidium bromide. On the basis of these observations, we concluded that BBM-928A bifunctionally intercalated with DNA in a manner similar to the bifunctional intercalation of echinomycin.
D000903:Antibiotics, Antineoplastic; D055598:Chemical Phenomena; D002621:Chemistry; D003090:Coliphages; D004270:DNA, Circular; D004278:DNA, Superhelical; D004279:DNA, Viral; D004448:Echinomycin; D009690:Nucleic Acid Conformation; D011804:Quinolines; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014783:Viscosity
D000903:Antibiotics, Antineoplastic; D004270:DNA, Circular; D004278:DNA, Superhelical; D004279:DNA, Viral; D011804:Quinolines; D004448:Echinomycin; C027844:BBM-928