EVALUATION OF ZEAMATIN AS AN ANTIFUNGAL THERAPEUTIC

描述：（改编自申请人摘要）。 在过去三 几十年来，真菌感染的频率急剧增加， 免疫缺陷宿主的感染。 隐球菌属，念珠菌属， 曲霉菌和卡氏肺孢子虫是重要的机会致病菌 病原体，而球孢子菌属，组织胞浆菌属和孢子丝菌属的物种是 主要病原体。 真菌感染的治疗仅限于 包括阿替霉素B和唑类药物。 不幸的是， 阿替霉素B具有毒性，对唑类药物的临床耐药性正在增加。 这些观察结果强调了对新的抗真菌药物的需求。 Permatins是 在植物种子中发现的小蛋白质，与奇异果甜蛋白同源， 第5组病程相关蛋白。 Zeamatin，模式家族成员 具有有效的体外杀真菌活性， 病原真菌 在本阶段I SBIR中，PI建议测试 在三个国家中，泽马丁作为人类抗真菌治疗剂的可行性 具体目标。 目的一：在cGMP条件下从高纯度玉米中纯化玉米素。 赖氨酸玉米粉 目的二：检测纯化的玉米黄素在体内阴道中的作用 念珠菌病小鼠模型。目的三：对纯化的玉米素进行体内试验 系统性念珠菌病小鼠模型。 这些结果将决定 玉米黄素在体内具有抗真菌活性， 开发玉米素作为人类治疗药物。 拟议商业应用：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