ZEAMATIN, 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。 感染宿主的真菌病 主要是机会性感染的结果;隐球菌属， 念珠菌、曲霉菌和卡氏肺孢子虫是重要致病菌 剂. 目前真菌感染的治疗方法受到少数 治疗选择 可用的药物包括阿替霉素B和a 各种各样的azole。 不幸的是，阿替霉素B对人类有毒， 对唑类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明确需求。 Permatins是一个家族 在植物种子中发现的小蛋白质。 Zeamatin，模式家族 从玉米中分离的成员，引起真菌膜透性变化 并且具有有效的体外杀真菌活性， 人类病原真菌 在本阶段I SBIR中，PI建议测试 玉米素作为抗真菌治疗剂的可行性。 首先， 克玉米蛋白将被纯化至表观均一性。 二是 玉米大黄素对卡氏肺孢子虫体内感染作用 将被确定。第三，将测试玉米素对 皮肤癣菌，须癣毛癣菌颗粒变种在体内 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.