Anthramycin, a new type of DNA-inhibiting antibiotic: Reaction with DNA and effect on nucleic acid synthesis in mouse leukemia cells

Autor: Vincent H. Bono, Kurt W. Kohn, Herbert E. Kann
Rok vydání: 1968
Předmět:
Zdroj: Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis. 155:121-129
ISSN: 0005-2787
DOI: 10.1016/0005-2787(68)90342-0
Popis: 1. Anthramycin, a new antibiotic and potent cytotoxic agent, was found to inhibit selectively RNA and DNA synthesis by mouse leukemia cell suspensions. Unlike actinomycin, anthramycin did not inhibit RNA much more than DNA synthesis. 2. The possibility that anthramycin may inhibit DNA primer function by direct interaction with DNA was investigated. Anthramycin was observed to react with purified DNA in solution, producing changes in DNA melting temperature and buoyant density, and undergoing a change in absorption spectrum. 3. Unlike most DNA-binding antibiotics, anthramycin reacts relatively slowly with DNA, so that it is easy to follow the kinetics of the reaction. 4. The antibiotic exhibits a high degree of preference for reaction with helical DNA. It does react with heat-denatured DNA but much more slowly. No reactions with soluble RNA or deoxyribonucleotides were detected. 5. The complex between anthramycin and helical DNA was not decomposed by alcohol precipitation, ultracentrifugal banding in concentrated CsCl, heating to the DNA melting temperature, or denaturation of the DNA by exposure to high pH. 6. The firmness of the binding, the slowness of the reaction, and the absence of any obvious structural features to account for firm binding suggest that anthramycin binds to DNA by means of covalent bonds.
Databáze: OpenAIRE