IN VITRO SCREEN FOR FUNGAL GLUCAN SYNTHASE INHIBITORS

真菌葡聚糖合酶抑制剂的体外筛选

• 批准号: 3489704
• 负责人: Claude P Selitrennikoff
• 金额: $ 3.28万
• 依托单位: MYCOLOGICS, INC.
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-02-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3489704
• 关键词: antifungal agents; antimetabolites; bioassay; drug screening /evaluation; enzyme activity; enzyme inhibitors; glucans; method development; microorganism metabolism; scintillation counter

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.

真菌在医学和经济上都非常重要，有助于 废物、腐败和疾病。 治疗人类真菌疾病， 特别是在免疫缺陷患者中，例如那些患有 艾滋病毒/艾滋病，由于实际上缺乏 临床上有用的药物。 丝状真菌的形态发生和生长是 多糖聚合物和其它材料的直接结果是 依次沉积在每个菌丝顶端，导致形成一个 成熟细胞壁 单元壁组装导致壁包含 几丁质、β（1-3）葡聚糖和其它β-和α-连接的葡聚糖， 蛋白质和脂质。 一个关键的步骤，也许是关键的一步， 细胞壁组装是β（1，3）葡聚糖的合成，其 随后进入细胞壁。 虽然有一些 在已知的葡聚糖合成酶抑制剂中， 这妨碍了它们的临床应用。 我们建议发展一个 β（1，3）抑制剂高通量、灵敏、特异性筛选 葡聚糖合成酶活性。 此屏幕可用于识别小说 用于最终治疗用途的抑制剂。

项目成果

A high throughput in vitro assay for fungal (1,3)beta-glucan synthase inhibitors.

真菌 (1,3)β-葡聚糖合酶抑制剂的高通量体外测定。

• DOI: 10.7164/antibiotics.47.1001
• 发表时间: 1994
• 期刊: The Journal of antibiotics
• 作者: Taft,CS;Enderlin,CS;Selitrennikoff,CP
• 通讯作者: Selitrennikoff,CP