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

Biochemistry. 1980 Nov 25;19(24):5537-42. doi: 10.1021/bi00565a012.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibiotics, Antineoplastic*
  • Chemical Phenomena
  • Chemistry
  • Coliphages
  • DNA, Circular
  • DNA, Superhelical
  • DNA, Viral*
  • Echinomycin
  • Nucleic Acid Conformation
  • Quinolines
  • Spectrometry, Fluorescence
  • Structure-Activity Relationship
  • Viscosity

Substances

  • Antibiotics, Antineoplastic
  • DNA, Circular
  • DNA, Superhelical
  • DNA, Viral
  • Quinolines
  • Echinomycin
  • BBM-928