Mechanism of Action of Chromomycin A3

Abstract
Chromomycin As, an antibiotic and antitumor substance produced by Strptomyces griseus No. 7 (ATCG 13273), was shown to be a potent inhibitor of RNA polymerase [EC 2.7.7.6] reaction. About 50% inhibition was achieved in the presence of 0.1 (μg. of chromomycin As in the 0.25 ml. of the reaction mixture containing 28 (μg. of native calf thymus DNA. The inhibition was reduced by prior heat denaturation of the template DNA. The antibiotic did not inhibit the poly A synthesis primed by denatured DNA, or the formation of AU copolymer with deoxyAT copolymer as template. Thus, the mechanism of action of chromomycin A3 is similar to that of actinomycin D. From the studies with various derivatives of chromomycin A,, it was concluded that the presence of sugar moiety is necessary for its effect as inhibitor of RNA synthesis.

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