EVALUATION OF ZEAMATIN AS AN ANTIFUNGAL THERAPEUTIC

描述：(改编自申请人摘要)。在过去三年中 几十年来，真菌的发生频率急剧增加 免疫缺陷宿主的感染。隐球菌属、念珠菌属、 曲霉和卡氏肺孢子虫是重要的机会性致病因素 球孢子虫、组织胞浆菌和孢子丝菌 重要的主要病原体。真菌感染的治疗仅限于 几种选择，包括两性霉素B和唑类。不幸的是， 两性霉素B具有毒性，临床上对唑类药物的耐药性正在增加。 这些观察结果强调了新的抗真菌药物的必要性。Permatins是 在植物种子中发现的小蛋白，与thaumatin和thaumatin同源 第5组致病相关蛋白。Zeamatin，典型的家庭成员 从玉米中提取，对人类有很强的体外杀菌活性 病原真菌。在此阶段I SBIR中，PI建议测试 玉米素作为人类抗真菌药物的可行性 明确的目标。目的一：在cGMP条件下从高糖中分离纯化玉米素 赖氨酸玉米粉。目的二：在活体阴道内检测纯化的玉米素 念珠菌病小鼠模型。目的三：在体内测试纯化的玉米素 系统性念珠菌病小鼠模型。这些结果将决定是否 玉米素在体内具有抗真菌活性，将是 玉米素作为人类治疗药物的发展。 建议的商业应用：不可用

DESCRIPTION: (Adapted from applicant's Abstract). During the last three decades there has been a dramatic increase in the frequency of fungal infections in immunodeficient hosts. Species of Cryptococcus, Candida, Aspergillus and Pneumocystis carinii are important opportunistic causative agents, while species of Coccidioides, Histoplasma and Sporothrix are important primary pathogens. Treatment of fungal infections is limited to a few options including amphotericin B and azoles. Unfortunately, amphotericin B is toxic and clinical resistance to azoles is increasing. These observations underscore the need for new antifungals. Permatins are small proteins found in seeds of plants and have homology to thaumatin and Group 5 pathogenesis-related proteins. Zeamatin, the type family member from corn, has potent in vitro fungicidal activity against human pathogenic fungi. In this Phase I SBIR the PI proposes to test the feasibility of zeamatin as an antifungal therapeutic in humans in three specific aims. Aim One: purify zeamatin under cGMP conditions from hi- lysine cornmeal. Aim Two: Test purified zeamatin in an in vivo vaginal candidiasis murine model. Aim three: Test purified zeamatin in an in vivo systemic candidiasis murine model. These results will determine whether zeamatin has antifungal activity in vivo and will be an important step in the development of zeamatin as a therapeutic for use in humans. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE