IN VITRO ASSAYS FOR FUNGAL TRANSDUCTION KINASES

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DESCRIPTION: (Adapted from applicant's Abstract). The fungal cell wall protects the organism against a hostile environment and relays signals for infection of a likely plant, animal, or human host. The cell wall of fungi is synthesized at each hyphal apex or a yeast bud by a complex regulatory and assembly sequence. Two signal transduction kinases with homology to bacterial two-component osmosensors are essential for cell wall assembly and cell viability. The corresponding gene products are absent in humans and other mammals, thus, providing unique targets for antifungal antibiotics. It is proposed to develop in vitro enzyme assays to screen compounds for inhibitors of each kinase activity. The specific aims of this proposal are: 1. To develop an in vitro assay for the Candida histidine kinase-1 two-component kinase activity from Candida albicans. 2. To develop an in vitro assay for the suppressor null-7 kinase cognate from C. albicans. 3. To test samples on a pilot scale for inhibitors of the chk1 and skn7 kinase activities. The development of these novel assays will lead to the discovery of new classes of antifungal compounds.