CHROMOMYCIN A3 STUDIES IN AQUEOUS SOLUTIONS . SPECTROPHOTOMETRIC EVIDENCE FOR AGGREGATION AND INTERACTION WITH HERRING SPERM DEOXYRIBONUCLEIC ACID

Chromomycin A3 is an antibiotic with antitumor activity and is known to exhibit an inhibitory effect on the deoxyribonucleic acid dependent ribonucleic acid and deoxyribonucleic acid synthesis. The effects of environmental factors on the absorption spectrum and optical rotatory dispersion of the antibiotic were examined, and chromomycin A3 molecules were found to form aggregates of various sizes. Concentration and magnesium ion were found to cause characteristic changes in the absorption spectrum due to the shifts of the equilibrium positions of various molecular forms present in aqueous solutions. The aglycone, chromomycinone, was studied in the same way and found not to exhibit any aggregative properties on spectrophotometric observations. The mode of interaction of chromomycin A3 with herring sperm deoxyribonucleic acid in the presence of magnesium ion was studied with the aid of spectrophotometric techniques. The data suggest that in agreement with the aggregative tendency of chromomycin A3 found in this study, the antibiotic molecules bind deoxyribonucleic acid to form an aggregative state through the bridging with magnesium ion. In this state chromomycin A3 molecules are believed to be preferentially bound to a site adjacent to those already occupied in an antibiotic-deoxyribonucleic acid complex. The comparative study of the binding with deoxyribonucleic acid was made by the use of a series of the antibiotic analogs and the interacting tendency was shown to be completely parallel with their biological activity. The direct involvement of the side-chain sugar moieties in the binding to deoxyribonucleic acid was indicated. The interaction study was also extended to transfer ribonucleic acid, mononucleotides, amino acids, and bovine serum albumin, and the cooperative binding suggested for deoxyribonucleic acid was found not to occur with transfer ribonucleic acid. © 1969, American Chemical Society. All rights reserved.