Error catastrophe using mutagenic nucleoside analogues can be employed as a strategy for inhibiting viral replication. Such ribonucleoside analogues would have to possess a degenerate base and be incorporated into the viral genome. To this end, a library of N-6-hydroxy, methoxy or amino adenosine analogues was prepared. These analogues have significantly altered tautomeric constants (K-T approximate to 10-100) when compared to the native nucleotides (K-T approximate to 10(4)-10(6)). Minor tautomers have been implicated in giving rise to mutations and a modest increase in the viral mutation rate could potentially result in reduced viability of progeny viruses, thereby inhibiting viral replication.
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Univ Washington, Dept Pathol, Joseph Gottstein Mem Canc Res Lab, Seattle, WA 98195 USAUniv Washington, Dept Pathol, Joseph Gottstein Mem Canc Res Lab, Seattle, WA 98195 USA
Anderson, JP
Daifuku, R
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机构:Univ Washington, Dept Pathol, Joseph Gottstein Mem Canc Res Lab, Seattle, WA 98195 USA
Daifuku, R
Loeb, LA
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机构:Univ Washington, Dept Pathol, Joseph Gottstein Mem Canc Res Lab, Seattle, WA 98195 USA