The fungal cell wall protects the organism against a hostile environment and relays signals for invasion and infection of a likely plant, animal, or human host. The cell wall of fungi is synthesized at each hyphal apex in a complex assembly sequence. The fungal wall affords a clear and discernible difference between fungi and their human host, providing an experimental target for antifungal antibiotics. In this Phase I SBIR application, we propose to develop two novel screens that target the activity of two protein kinases essential for cell-wall assembly, colonial temperature sensitive-1 serine/threonine kinase and protein kinase C1. We will accomplish this in three specific aims: 1) Specific aim one: develop in vitro enzyme assay for the colonial temperature sensitive-1 protein kinase, 2) Specific aim two: develop an in vitro enzyme assay for Protein Kinase C1 activity, 3) Specific aim three: screen natural samples on a pilot scale. These assays will lead to the identification of novel antifungal compounds that inhibit the regulation of cell-wall biosynthesis. Such drugs are likely to be safe and effective human therapeutics.
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