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A reverse transcriptase activity, extracted from virus-transformed cells, is activated by very low concentrations of nonionic detergents. These same detergents also significantly reduce the effectiveness of certain rifamycin derivatives as inhibitors of the polymerase activity when the detergents are present at micelle-forming concentrations.

It is possible to design rifamycin derivatives which can distinguish between viral RNA-instructed DNA polymerase and other nucleotide polymerases.The discovery by Baltimore (1) and Temin and Mizutani (2) of a DNA polymerase which utilizes RNA as its template, and the enzyme's relatively specific association with oncogenic viruses, has opened a new area of research on possible chemotherapy for virus-related cancers. Certain rifamycin derivatives serve as effective antibiotics by inhibiting the bacterial DNA-dependent RNA polymerase at concentrations which do not inhibit the analogous mammalian enzyme (3). This specific inhibition of a particular polymerase has encouraged attempts to test many rifamycin derivatives as inhibitors of the viral RNA-instructed DNA polymerase (RDP) (4-9). Most of these derivatives were found to be inhibitors of the viral DNA polymerase, but at considerably higher concentrations than required to inhibit the bacterial RNA polymerases.Recently L. G. Silvestri and coworkers postulated that the so-called "Class C" (10, 11) rifamycin derivatives, i.e., rifamycins containing large hydrophobic side chains, are nonspecific inhibitors of enzymes in general, particularly for nucleotide polymerases other than bacterial RNA polymerases (12). This conclusion is drawn from the observation that a few "Class C" rifamycin derivatives inhibit several nucleotide polymerases at comparable concentrations. It has been our intention to further investigate this lack of inhibitory specificity among hydrophobic rifamycin derivatives. Several new derivatives have been synthesized in this laboratory to systematically study inhibition of the viral enzyme as a function of size (13) and hydrophobobicity (14). We found that both of these characteristics are important for maximizing inhibition of the viral enzyme. When also tested against DNA-dependent DNA polymerase (DDP) from Escherichia coli and DNA-dependent RNA polymerase (DRP) from E. coli, most, but not all, of the rifamycin derivatives we had tested showed little or no specificity for the viral enzyme. MATERIALS AND METHODSRifamycin Derivatives. The rifAmycin derivatives were synthesized as previously described (9, 13, 14). The structures and codes are given in Table 1

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