Inhibition of Moloney murine leukemia virus reverse transcriptase by partially 5-thiolated polyuridylic acid.

ABSTRACT

Partially 5-thiolated polyuridylic acid (poly(U60,hs5U40)) is shown to be a potent inhibitor of Moloney murine leukemia virus Reverse Transcriptase (M-MuLV RT). The pattern of this inhibition is competitive, when either poly(A).(dT)16 or poly(C).(dG)16 as template-primer (variable substrate) are used, suggesting that the free enzyme interacts with the modified polynucleotide. Km and Ki values of 25 microM and 11 nM, respectively, were obtained in the presence of poly(A).(dT)16. The Ki value determined in the presence of poly(C).(dG)16 was 31 nM (Km = 22 microM). Inhibitory activities of the 5-thiolated oligouridylic acids, prepared from the polymer, depend on the chain-length. While the 30-mer showed the same activity as the intact polynucleotide, shorter oligonucleotide proved to be less active.