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A NOVEL SCREEN FOR INHIBITORS OF FUNGAL GPI-ANCHORING

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:
$10.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2002
资助国家:
美国
项目状态:
已结题
起止时间:
2002-02-15 至 2003-02-14

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中文摘要
翻译
描述(申请人提供):也许最显著的不同之处 真菌细胞和人类细胞之间的区别是真菌细胞被包裹在一堵墙里 这保护它们免受敌对的外部环境的影响。细胞壁扮演着一种 在真菌生理学的方方面面都起着积极的作用。事实上,人类细胞 缺乏细胞壁和潜在的生物合成和调节机制 造壁,提示靶向细胞壁合成和组装的药物 将是安全和特效的抗真菌药物。目前的治疗方法包括两性霉素 B和多种能够抑制膜上甾醇生物合成的唑类化合物。 不幸的是,两性霉素B对人类有毒,临床上对 偶氮类药物的数量正在增加。这些观察结果强调了新的 抗真菌药。 在此第一阶段SBIR应用中,我们建议开发一种新型屏幕,该屏幕 靶向真菌细胞壁组装的关键步骤,即 GPI类甘露糖蛋白的胞外锚定。这将会实现的 具体目标有两个:1)。一种检测血管紧张素转换酶抑制剂的筛选方法的研制 GPI-甘露糖蛋白锚定到细胞壁;金银花提取物的筛选 在Aim One中开发了使用该检测方法的抑制剂。 建议的商业应用:不可用
英文摘要
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
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