IN VITRO ASSAYS FOR FUNGAL TRANSDUCTION KINASES

描述：(改编自申请人摘要)。真菌细胞壁 保护生物体免受恶劣环境的侵袭，并传递信号 对于可能的植物、动物或人类宿主的感染。细胞壁 在每个菌丝顶端或酵母芽由一个复合体合成 调节和组装顺序。两种信号转导蛋白与 细菌双组分渗透传感器的同源性对于细胞来说是必不可少的 壁组装和细胞存活率。相应的基因产物是 在人类和其他哺乳动物中不存在，因此为 抗真菌抗生素。有人建议开发体外酶 用于筛选每种酶活性抑制剂的化合物的分析。这个 这项建议的具体目的是：1.建立一种体外试验 假丝酵母组氨酸激酶-1双组分的活性 白色念珠菌。2.建立抑制子的体外检测方法 Null-7同源蛋白来自白色念珠菌。3.在飞行员身上测试样品 Chk1和skn7激酶活性抑制剂的标度。这个 这些新的分析方法的发展将导致新的 抗真菌化合物的类别。

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.