IN VITRO SCREEN FOR FUNGAL GLUCAN SYNTHASE INHIBITORS

真菌在医学和经济上都非常重要，有助于 浪费、腐败和疾病。治疗人类真菌病， 尤其是在免疫缺陷患者中，例如患有 获得性免疫缺陷综合征，实际上是由于缺乏 临床上有用的药物。丝状真菌的形态发生和生长 多糖聚合物和其他材料的直接结果是 在每个菌丝顶端顺序沉积，导致形成一个 成熟的细胞壁。细胞壁组装导致含有 甲壳素，β(1-3)葡聚糖，以及其他β和α连接的葡聚糖， 蛋白质和脂类。真菌的关键一步，也许是关键的一步 细胞壁组装是β(1，3)葡聚糖的合成，其 随后结合到细胞壁中。尽管有一个数字 在已知的葡聚糖合成酶抑制剂中，每一种都存在各种缺陷 这就排除了它们的临床应用。我们建议开发一种 高通量、灵敏、特异的β(1，3)抑制物筛选 葡聚糖合成酶活性。这个屏幕可以用来识别小说 最终用于治疗用途的抑制剂。

Fungi are medically and economically very important, contributing to waste, spoilage and disease. Treatment of human fungal disease, especially in immunodeficient patients, for example those suffering from Acquired Immunodeficiency Syndrome, is hampered by the virtual lack of clinically useful drugs. Filamentous fungal morphogenesis and growth are the direct result of polysaccharide polymers and other materials being sequentially deposited at each hyphal apex, leading to the formation of a mature cell wall. Cell-wall assembly results in a wall containing chitin, beta(1-3) glucan, and other beta- and alpha-linked glucans, proteins and lipids. A key step, perhaps the key step, in fungal cell-wall assembly is the synthesis of beta(1,3) glucan, and its subsequent incorporation into the cell wall. Although there are a number of known glucan synthase inhibitors, each suffers from a variety of flaws that precludes their clinical use. We propose to develop a high-throughput, sensitive, specific screen for inhibitors of beta(1,3) glucan synthase activity. This screen can be used to identify novel inhibitors for eventual therapeutic use.