Screen for Antifungal RNA Polymerase II Inhibitors

Two factors have contributed to the urgent need for effective new antifungal agents - the rising insystemic yeast and mold infections, especially in immunocompromised individuals, and the current lacboth fungicidal and relatively free of deleterious side effects. The aim this research is to identifinhibitors of fungal RNA polymerase II, the enzyme required for the synthesis of all nuclear-encodedfor targeting RNA polymerase II is based on its requirement for fungal viability, genetic and biochedemonstrating mechanistic differences between fungal and mammalian RNA polymerase II transcription alack of prior research into antifungal therapeutics targeted specifically against RNA polymerase II.steps toward realizing the aim of this proposal: l) purification of RNA polymerase II from pathogeniquantity to support high-throughput screening; 2) development of a robust, high-throughput biochemiccompounds that selectively inhibit fungal, but not human, RNA polymerase II; 3) adaptation of the asrequirements of defined chemical and natural product extract library screening.