Polyinosinic acids containing methyl and sulphur substitutions are potent inhibitors of reverse transcriptase. Substitution of sulphur for oxygen at the 6 position produces significant effects on the properties of polyinosinic acid: the kinetics of inhibition change from competitive to mixed-type and the inhibition constant falls by three orders of magnitude. In contrast, 1-methyl substitution produces no such effects. Poly(1-methyl-6-thioinosinic acid) or poly(msI) inhibits irreversibly, inhibiting all ten reverse transcriptases tested under a variety of assay conditions. In cell culture test systems, poly(msI) is capable of blocking both infection by non-transforming viruses and transformation by a sarcoma virus. The presence of poly(msI) in a preinfected culture results in the production of non-infectious virus particles lacking reverse transcriptase activity.


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