IDENTITY AND ROLE OF NOVEL GI PEPTIDES IN HOST DEFENSE

长期目标是(1)确定相关的新型候选药物

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.