Chymotrypsin C in pancreatitis

描述（由申请人提供）：本申请是对NIH通知no - od -09-058的回应，标题为“NIH宣布竞争性修订申请的恢复法案资金可用性”。这项竞争性修订资助旨在鉴定消化酶凝乳胰蛋白酶C的新型肽抑制剂。亲本资助研究凝乳胰蛋白酶C如何调节其他消化酶的激活和降解，以及凝乳胰蛋白酶C的突变如何增加人类慢性胰腺炎的风险。高特异性胰凝乳蛋白酶C抑制剂的可用性将有助于实现母基金中概述的特定目标，并提高研究计划的整体速度。我们建议利用噬菌体展示技术筛选候选抑制剂；利用合成和天然胰凝乳蛋白酶C底物对这些抑制剂进行表征，并确定与胰凝乳蛋白酶C共结晶抑制剂特异性抑制的结构基础。

DESCRIPTION (provided by applicant): This application is in response to NIH notice NOT-OD-09-058, entitled "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". This competitive revision grant proposes to identify novel peptide inhibitors for the digestive enzyme chymotrypsin C. The parent grant investigates how chymotrypsin C regulates activation and degradation of other digestive enzymes and how mutations in chymotrypsin C increase the risk of chronic pancreatitis in humans. The availability of a highly specific chymotrypsin C inhibitor would facilitate the accomplishment of the specific aims outlined in the parent grant and enhance the overall tempo of the research program. We propose to use phage display technology to select candidate inhibitors; to characterize these inhibitors using both synthetic and natural chymotrypsin C substrates and to determine the structural basis of specific inhibition by co-crystallizing inhibitors with chymotrypsin C. PUBLIC HEALTH RELEVANCE: The present grant proposal intends to develop novel inhibitors against human chymotrypsin C, a digestive enzyme, which plays an important role in regulating other digestive enzymes and has been linked to the development of chronic pancreatitis, an often debilitating disease. The results can advance the development of novel diagnostic and therapeutic interventions for human pancreatitis.