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子 人类分子，并定义其结构和机制 行动。 该提案涉及男性抗菌肽 生殖道，目前该领域的信息非常少 存在。 假设。正常人精液中含有潜在的蛋白质 由丝氨酸和天冬氨酰激活的抗菌结构域 正常精液中发现的蛋白酶。 所得肽（“altruins”） 可以保护女性免受引入细菌的感染 性交时的阴道。 具体目标。 1）。 鉴定和表征抗菌肽 及其在人类精液中的前体。 2）。 为了确定如何 这些肽的前体经过处理并确定负责的 蛋白酶。 3）。 为了测试这些肽对沙眼衣原体、大肠杆菌的抵抗力， STD 病原体和正常阴道菌群。 4）。合成选定的 精肽，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 渗透色谱法、制备型电泳和 RP-HPLC 净化正常精液和调节 pH 值的精液中的抗菌成分。 将测试这些级分的抗菌活性，并且 它们所含的活性效应分子将被纯化至均质， 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。 据 CDC 估计，其他性传播疾病 比艾滋病给国家每年医疗保健增加 100 亿美元还要多 I 成本。 拟议的研究可能会带来治疗性病的新方法 预防。