ALTRUINS, NATURAL ANTIBIOTICS OF THE MALE GENITAL TRACT

ALTRUINS，男性生殖道的天然抗生素

• 批准号: 6163998
• 负责人: ROBERT IRVING LEHRER
• 金额: $ 27.92万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-15 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6163998
• 关键词: Chlamydia trachomatis; Escherichia coli; antibiotics; aspartic endopeptidases; clinical research; high performance liquid chromatography; human subject; laboratory rabbit; male reproductive system; monoclonal antibody; protein biosynthesis; protein purification; protein sequence; semen; serine proteinases; sexually transmitted diseases; vagina

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.

长期目标。 发现内源性抗菌效应器 人类的分子，并定义其结构和机制 行动。 该建议涉及男性的抗菌肽 生殖道，目前很少的信息很少 存在。 假设。正常的人类精液含有潜在的蛋白质 被丝氨酸和天冬氨酸激活的抗菌结构域 在正常精液中发现的蛋白酶。 产生的肽（“利他蛋白”） 可以保护雌性免受引入的细菌感染 性交期间的阴道。 具体目标。 1）。 识别和表征抗菌肽 及其在人类精液中的前体。 2）。 确定如何 处理这些肽的前体并确定负责任的 蛋白酶。 3）。 测试这些肽针对沙眼梭状芽孢杆菌，大肠杆菌， 性病病原体和正常的阴道菌群。 4）。合成所选的 精确的肽，并阐明其作用机理。 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至 净化正常和pH条件精液的抗菌成分。 这些馏分将测试用于抗菌活性，并 它们所包含的主动效应分子将被纯化为均匀性， 测序，合成和研究。 健康相关性。 许多最常见的传染病 美国是性传播的。 根据疾病预防控制中心的估计，其他 比艾滋病为美国的年度医疗保健增加了100亿美元 费用。 拟议的研究可能导致性病的新方法 预防。