A NOVEL SCREEN FOR INHIBITORS OF FUNGAL GPI-ANCHORING

真菌 GPI 锚定抑制剂的新型筛选

• 批准号: 6442431
• 负责人: Claude P Selitrennikoff
• 金额: $ 10万
• 依托单位: MYCOLOGICS, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-15 至 2003-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6442431
• 关键词: antifungal agents; aquatic organism; drug design /synthesis /production; drug discovery /isolation; drug screening /evaluation; enzyme linked immunosorbent assay; fungal proteins; glycosylphosphatidylinositols; high throughput technology; mannose; phospholipid inhibitor

DESCRIPTION (provided by applicant):Perhaps the most striking difference between fungal cells and human cells is that fungal cells are encased in a wall that protects them from a hostile external environment. The cell wall plays a dynamic role in all aspects of fungal physiology. The fact that human cells lack a cell wall and the underlying biosynthetic and regulatory machinery to make the wall, suggests that drugs targeting cell-wall synthesis and assembly will be safe and specific antifungals. Current treatments include Amphotericin B and a variety of azoles that inhibit membrane-sterol biosynthesis. Unfortunately, Amphotericin B is toxic to humans and clinical resistance to azoles is increasing. These observations underscore the clear need for new antifungals. In this Phase I SBIR application, we propose to develop a novel screen that targets an essential step in fungal cell-wall assembly, namely, the extracellular anchorage of GPI-class mannoproteins. This will be accomplished in two specific aims: 1). Development of a screen to detect inhibitors of GPI-mannoprotein anchoring into the cell wall; 2). Screening of extracts for inhibitors using the assay developed in Aim One. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（由申请人提供）：也许是最显着的区别 真菌细胞和人类细胞之间的区别在于真菌细胞被包裹在墙壁中 保护他们免受敌对的外部环境的影响。细胞壁起着 在真菌生理学各个方面的动态作用。 The fact that human cells 缺乏细胞壁和潜在的生物合成和调节机制 制造细胞壁，表明靶向细胞壁合成和组装的药物 will be safe and specific antifungals. Current treatments include Amphotericin B和多种唑类可抑制膜甾醇生物合成。 不幸的是，两性霉素 B 对人类有毒，临床上对它产生耐药性 唑类正在增加。这些观察结果强调了明确需要新的 抗真菌剂。 在第一阶段 SBIR 应用中，我们建议开发一种新颖的屏幕 靶向真菌细胞壁组装的一个重要步骤，即 GPI 类甘露糖蛋白的细胞外锚定。这将实现 in two specific aims: 1). Development of a screen to detect inhibitors of GPI-mannoprotein anchoring into the cell wall; 2）。 Screening of extracts for inhibitors using the assay developed in Aim One. 拟议的商业应用：不可用