ALTRUINS, NATURAL ANTIBIOTICS OF THE MALE GENITAL TRACT

长期目标。 为了发现内源性抗菌效应物， 分子，并确定其结构和机制， 行动上 这项建议涉及男性的抗菌肽 生殖道，一个领域，目前非常少的信息， 存在. 假设。正常的人类精液含有蛋白质， 由丝氨酸和丝氨酸乙酰基激活的抗菌域 正常精液中的蛋白酶 所得肽（“altruins”） 可以保护女性免受细菌的感染， 性交时的阴道 具体目标。1）。 鉴定和表征抗菌肽 以及它们的前体。2）。 为了确定 这些肽的前体被加工，并确定负责的 蛋白酶3）。 为了测试这些肽对C. trachomatis、E.大肠杆菌， 性病病原体和正常阴道植物群。4）。为了合成选定的 精液肽，并阐明其作用机制。 方法. 我们将应用各种纯化程序，包括凝胶 渗透色谱、制备电泳和RP-HPLC， 纯化正常精液和pH调节精液的抗菌成分。 将测试这些级分的抗微生物活性，并且 它们所含的活性效应分子将被纯化至同质， 测序合成研究 健康相关性。 许多最常见的传染病， 美国是通过性传播的 根据CDC的估计， 比艾滋病给国家每年的医疗保健增加了100亿美元 成本 拟议的研究可能会导致新的方法性病 预防。

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.