BETA 1,3 GLUCAN MICROFIBRIL ASSEMBLY--ANTIFUNGAL TARGET

BETA 1,3 葡聚糖微纤维组件——抗真菌靶点

• 批准号: 2715730
• 负责人: WILLIAM GALBRAITH
• 金额: $ 9.94万
• 依托单位: ALPHA-BETA TECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-15 至 1999-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2715730
• 关键词: Candida albicans; antifungal agents; bioassay; cell wall; chitin; drug design /synthesis /production; glucans; gluconeogenesis; growth inhibitors; lead; method development; polysaccharides; protoplast /spheroplast

The essential fungal cell wall protects the organism against a hostile external environment and is synthesized in a complex assembly sequence. Since the fungal wall affords a clear and discernible difference between fungi and their human hosts, it provides a prime target for antifungal antibiotics. In this Phase I SBIR application, we propose to identify inhibitors of beta1,3 glucan microfibril assembly, a key step in the synthesis of the fungal cell wall, as potential antifungal lead compounds. We will accomplish this in three specific aims: Specific Aim One: To develop an existing assay to identify inhibitors of beta1,3 glucan microfibril assembly into a high-capacity assay. Specific Aim Two: To identify inhibitors of beta1,3 glucan microfibril assembly and screen for inhibition of Candida albicans cell growth and protoplast regeneration activities. Specific Aim Three: To test three beta1,3 glucan microfibril inhibitors for antifungal activity in an in vivo model of C.albicans infection. The identification of inhibitors of the assembly of beta1,3 glucan microfibrils will lead to the discovery of new classes of antifungal therapeutics for use in the treatment of human fungal infections. PROPOSED COMMERCIAL APPLICATION: Over the last few years the market for antifungal drugs has been one of the fastest growing markets for the pharmaceutical industry; 25% annual growth with the market total for 1996 of greater than $4.5 billion. This antifungal target and assay will lead to the discovery of novel antifungal compounds that have significant market potential.

基本的真菌细胞壁保护有机体免受有害物质的侵害。 外部环境，并在复杂的装配序列中合成。 由于真菌壁提供了一个明确的和可辨别的区别， 真菌及其人类宿主，它提供了抗真菌药物的主要目标， 抗生素 在该I期SBIR应用中，我们提出鉴定以下的抑制剂： β 1，3葡聚糖微纤维组装，这是合成β 1， 真菌细胞壁，作为潜在的抗真菌先导化合物。我们将 实现这一目标有三个具体目标： 具体目标一：开发一种现有的检测方法来鉴定抑制剂 的β 1，3葡聚糖微纤维组装成一个高容量的测定。 具体目标二：鉴定β 1，3葡聚糖微纤维的抑制剂 用于抑制白色念珠菌细胞生长的组装和筛选， 原生质体再生活性 具体目标三：测试三种β 1，3葡聚糖微纤维抑制剂 用于在白色念珠菌感染的体内模型中的抗真菌活性。 β 1，3葡聚糖组装抑制剂的鉴定 微纤维将导致发现新的抗真菌药物 用于治疗人真菌感染的治疗剂。 拟定商业应用： 在过去的几年里，抗真菌药物的市场一直是 制药行业增长最快的市场;每年增长25% 1996年市场总额超过45亿美元。这 抗真菌靶点和检测将导致发现新的 具有巨大市场潜力的抗真菌化合物。