Binding of actinomycin chromophore analogues to DNA.

Abstract

Five chromophore analogues of actinomycin, viz. phenoxazone (1), aminophenoxazone (2), N-acetylaminophenoxazone (3), N-methylaminophenoxazone (4), and actinocin (5), were synthesized. Of these compounds, only 2 and 4 were found to interact with DNA. The binding constants for these compounds, obtained by spectrophotometric titration, were of the same order of magnitude as that obtained with actinomycin-DNA interaction. The major difference between the binding of actinomycin and of the analogues to DNA was the lability of the complex of the latter compounds in the presence of Mg2+ ions. These observations have been interpreted to indicate intercalation of the chromophore analogues between successive base pairs of DNA. The spectra of actinocin were unaffected by the addition of DNA. The spectral changes indicative of an interaction between actinocin and DNA observed at low concentration of Mg2+ ions were abolished at high concentrations of these ions. The implications of these observations to the mechanism of actinomycin binding to DNA are discussed.