ZEAMATIN, 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。受感染宿主中的霉菌是 主要是机会性感染的结果；隐球菌的种类， 念珠菌、曲霉菌和卡氏肺孢子虫是重要的致病菌 探员们。目前对真菌感染的治疗仅限于少数几种 治疗选择。可用的药物包括两性霉素B和A 不同种类的氮唑。不幸的是，两性霉素B对人类有毒， 临床对氮唑类药物的耐药性正在增加。这些观察结果 强调对新的抗真菌药物的明确需求。Permatins是一个大家庭 在植物种子中发现的小蛋白质。Zeamatin，典型的家庭 从玉米中分离出的一种引起真菌膜通透性变化的成员 并具有很强的体外杀菌活性，可杀死大量 人类致病真菌。在此阶段I SBIR中，PI建议测试 玉米素作为抗真菌治疗药物的可行性。第一，一 一克玉米素将被提纯至表面均一。第二， 玉米素对卡氏肺孢子虫体内感染模型的影响 将会被确定。第三，玉米素将与 皮肤病原真菌致病变种毛癣菌的活体研究 局部感染模型。

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. Mycoses in compromised hosts are mainly the result of opportunistic infections; species of Cryptococcus, Candida, Aspergillus and Pneumocystis carinii are important causative agents. Current treatments for fungal infections are limited by few therapeutic options. Available drugs include amphotericin B and a variety of azoles. Unfortunately, amphotericin B is toxic to humans and clinical resistance to azoles is increasing. These observations underscore the clear need for new antifungals. Permatins are a family of small proteins found in seeds of plants. Zeamatin, the type family member isolated from corn, causes fungal membrane permeability changes and has potent in vitro fungicidal activity, killing a wide number of human pathogenic fungi. In this Phase I SBIR the PI proposes to test the feasibility of zeamatin as an antifungal therapeutic. First, one gram of zeamatin will be purified to apparent homogeneity. Second, the effect of zeamatin on Pneumocysits carinii in an in vivo infection model will be determined. Third, zeamatin will be tested against the dermatophyte, Trichophyton mentagrophytes var granulare in an in vivo topical infection model.