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On the interaction of chromomycin A 3 with calf thymus DNA in the presence of metal cations at different pH values
Author(s) -
Weinberger Sarah,
Shafer Richard,
Berman Elisha
Publication year - 1988
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360270510
Subject(s) - chemistry , divalent , dna , titration , metal , chromomycin a3 , inorganic chemistry , binding site , stereochemistry , crystallography , biochemistry , organic chemistry , heterochromatin , chromatin
The interactions of the antitumor antibiotics, chromomycin A 3 , with a variety of metal cations in the pH range of 3.0–8.5 were systematically studied by CD, absorption, and 1 H‐nmr spectroscopies. Results were compared with those obtained in the presence of increasing amounts of calf thymus DNA. The negatively charged chromomycin A 3 , pK a 6.3, forms aggregates that become ordered and smaller in size, in the presence of variety of metal cations. Spectrophotometric titrations have shown that binding of the neutral drug to DNA at pH 4.5 does not require divalent cations, although the strength of the binding is greatly enhanced in their presence. At higher pH values (> 7.0) and low DNA/drug ratio ( > 20), the metal cations are necessary to induce the binding between chromomycin A 3 and DNA. At higher DNA/drug ratios (> 100: 1), an appreciable proportion of the drug is bound even in the absence of divalent cations. Its binding affinity to the DNA is enhanced in the presence of these cations and at low pH values. Therefore, we conclude that chromomycin A 3 binds in two related modes, in the presence and in the absence of divalent cations. The spectral data accumulated indicate the metal cation is involved in the binding of the drug to the DNA by forming a drug–metal–DNA ternary complex.