IDENTITY AND ROLE OF NOVEL GI PEPTIDES IN HOST DEFENSE

长期目标是（1）确定与药物相关的新型候选药物 以magainin类肽为原料，具有潜在的抗菌、抗病毒和 具有GI相关应用的抗炎活性，和（2） 推进我们对内源性膜的作用和机制的认识， 通道形成肽。 Zasloff描述了爪蟾抗菌肽，一种从哺乳动物中分离的21-27个氨基酸的肽， 青蛙皮，具有显著的抗菌，抗真菌和抗寄生虫 活动这些生物活性肽是一种诺埃尔脊椎动物宿主 防御系统，通过膜离子通道形成机制起作用。新 我们实验室的免疫学证据表明， 存在于青蛙的胃肠道中，指出它们在胃肠道功能中的作用， 新型胃肠道疗法的潜力。 我们的具体目标是绘制哺乳动物胃肠道的magainin样 缩氨酸我们将使用针对特定肽的抗体来检测 结构相关的分子和敏感的抗微生物生物测定， 指导纯化和帮助发现新分子。 将对分离的肽进行测序，并合成肽， 确认真实性和扩大生物测试。拟定研究 可以导致对爪蟾抗菌肽化合物的理解的重大进展， 胃肠道治疗和宿主防御的新方法。

Long-range objectives are (1) to identify novel drug candidates related to magainin class of peptides with potential antibacterial, antiviral and anti-inflammatory activity that have GI-related applications, and (2) advance our knowledge of the role and mechanisms of endogenous membrane channel forming peptides. Zasloff described the magainins, 21-27 amino acid peptides isolated from frog skin, with remarkable antibacterial, antifungal, and antiparasitic activities. These biologically active peptides are a noel vertebrate host defense system, acting by membrane ion channel forming mechanisms. New immunological evidence from our labs suggest the margainins are widely present in the frog's GI tract, pointing to their role in GI function and the potential of novel GI therapeutics. Our specific aim is to map the mammalian GI tract for magainin-like peptides. We will use antibodies to specific peptides to detect structurally related molecules and sensitive anti-microbial bioassays to guide purification and aid discovery of novel molecules. Isolated peptides will be sequenced and synthetic peptides made to confirm authenticity and biological testing expanded. Proposed studies can lead to major advances in understanding magainin compounds and open new approaches to GI therapeutics and host defense.