NOVEL ANTIFUNGAL SCREEN--CELL WALL REGULATION INHIBITORS

描述(改编自申请人的摘要)：真菌细胞 WALL保护有机体免受恶劣环境的伤害，并传递 可能的植物、动物或人类入侵和感染的信号 主持人。真菌的细胞壁是在每个菌丝顶端合成的 复杂的装配序列。真菌壁提供了一个清晰和 真菌和它们的人类宿主之间的明显区别，提供了 抗真菌抗生素的实验靶标。在此阶段I SBIR中 应用程序，我们建议开发两个新的屏幕，以 细胞壁组装所必需的两种蛋白激酶的活性， 殖民地温度敏感型-1丝氨酸/苏氨酸激酶和蛋白质 蛋白激酶C_1。我们将通过三个具体目标来实现这一点：1)具体目标 目的一：建立群体温度的体外酶分析方法 敏感-1蛋白激酶，2)特异性目标二：建立一种体外 蛋白激酶C1活性的酶测定法，3)特定目标3： 在中试规模上筛选天然样品。这些化验结果将导致 新型抗真菌化合物的鉴定 细胞壁生物合成的调控。这种药物很可能是安全的。 和有效的人类疗法。

DESCRIPTION (Adapted from the applicant's abstract): 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.