This preclinical study explores various inhibitors of the AMV RNA-directed DNA polymerase as a potential approach to scientific chemotherapy for nucleic acid-directed diseases.
DNA and RNA polymerases and their templates play a central role in the control of gene expression. As an approach to a scientific chemotherapy to control nucleic acid-directed disease, we have used the highly purified RNA-directed DNA polymerase of the avian myeloblastosis virus (AMV) as a test enzyme to search for inhibitors of DNA polymerase. Three kinds of inhibitors with different mechanisms of action were studied: 1) rifamycin SV derivatives; 2) polycyclic amines; and 3) homopolymers composed of 2′O-methyl and 2′-O-ethyl substituted poly(A), poly(U), poly(I), and poly(C). The biological activity in vitro and in vivo of these inhibitors and their mechanisms of action are discussed.
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Green et al. (1974) studied this question.
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