ALTRUINS, NATURAL ANTIBIOTICS OF THE MALE GENITAL TRACT

长期目标。发现内源性抗菌效应物 人类的分子，并定义它们的结构和机制 行动。这项建议涉及男性的抗菌肽。 生殖道，这是一个目前信息非常少的领域 是存在的。 假设。正常人精液中含有潜伏的蛋白质 丝氨酸和天冬氨酸激活的抗菌域 正常精液中的蛋白水解酶。由此产生的多肽(“altruins”) 可以保护女性免受细菌感染 性交时的阴道。 明确的目标。1)。抗菌肽的鉴定与鉴定 以及它们的前体在人类精液中。2)。以确定如何 这些多肽的前体被处理并识别出负责的 蛋白酶。3)。为了测试这些多肽对沙眼衣原体、大肠杆菌的作用， 性病病原体，以及正常的阴道菌群。4)。合成选定对象 并阐明其作用机制。 方法：研究方法。我们将应用各种净化程序，包括凝胶 渗透层析法、制备电泳法和反相高效液相色谱法 提纯正常精液和pH调节精液中的抗菌成分。 这些组分将进行抗菌活性测试， 它们包含的活性效应器分子将被提纯到均一状态， 测序、合成和研究。 与健康相关。世界上许多最常见的传染病 美国人是性传播的。根据疾控中心的估计，性传播疾病其他 艾滋病为国家每年的医疗保健增加了100亿美元 成本。拟议的研究可能会带来治疗性病的新方法。 预防措施。

Long term objectives. To discover the endogenous antimicrobial effector molecules of humans, and to define their structures and mechanisms of action. This proposal deals with antimicrobial peptides of the male genital tract, an area where remarkably little information currently exists. Hypotheses. Normal human semen contains proteins with latent antimicrobial domains that are activated by serine and aspartyl proteases found in normal semen. The resulting peptides ("altruins") can protect the female from infection by bacteria introduced into the vagina during intercourse. Specific aims. 1). To identify and characterize antimicrobial peptides and their precursors in human semen. 2). To ascertain how the precursors of these peptides are processed and identify the responsible proteases. 3). To test these peptides against C. trachomatis, E. coli, STD pathogens, and normal vaginal flora. 4). To synthesize selected seminal peptides, and elucidate their mechanisms of action. Methods. We will apply various purification procedures, including gel permeation chromatography, preparative electrophoresis and RP-HPLC to purify the antimicrobial components of normal and pH conditioned semen. These fractions will be tested for antimicrobial activity, and the active effector molecules they contain will be purified to homogeneity, sequenced, synthesized, and studied. Health relatedness. Many of the most common infectious diseases in the U.S. are sexually transmitted. According to CDC estimates, STDs other than AIDS add 10 billion dollars to the nation's annual health care I costs. The proposed studies could lead to novel approaches for STD prophylaxis.