Chymotrypsin C in pancreatitis

胰凝乳蛋白酶 C 在胰腺炎中的作用

基本信息

批准号：
7809165
负责人：
Miklos Sahin-Toth
金额：
$ 56.63万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7809165
关键词：
Acinar Cell Acinus organ component Adenoviruses Advanced Development Affect Apoptosis Applications Grants Biochemical Biological Carboxypeptidase Cell Line Cells Classification Collaborations Data Defect Development Disease Disease model Elastases Embryo Endoplasmic Reticulum Enzyme Activation Enzymes Funding Future Grant Hereditary Disease Human Human Genetics Inflammation Inflammatory Investigation Kidney Lectin Light Link Measures Mediating Methodology Methods Molecular Mus Mutation N-Glycosylation Site Nuclear Nuclear Translocation Pancreas Pancreatitis Parents Pathway interactions Peptide Hydrolases Peptides Phage Display Pharmacologic Substance Play Post-Translational Protein Processing Prevention therapy Proteins Quality Control Rattus Reagent Recombinants Recovery Regulation Research Research Design Risk Risk Factors Role Structure Substrate Specificity System Technology Therapeutic Intervention Transfection Trypsin United States National Institutes of Health Variant base chronic pancreatitis chymotrypsin chymotrypsin C chymotrypsin-like enzyme chymotrypsinogen C cost design endoplasmic reticulum stress genetic association genetic risk factor glycosylation inhibitor/antagonist insight mutant novel novel diagnostics parent grant programs public health relevance research study response small molecule transcription factor

项目摘要

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.

描述（申请人提供）：此申请是响应NIH通知NOT-OD-09-058，标题为“ NIH宣布恢复ACT资金用于竞争性修订申请”。这项竞争性修订赠款建议鉴定消化酶胰蛋白酶蛋白酶的新型肽抑制剂C.父母赠款研究了辣椒蛋白蛋白酶C如何调节其他消化酶的激活和降解，以及辣椒素C中的突变如何增加人类慢性胰腺炎的风险。高度特异性的chymotrypsin C抑制剂的可用性将有助于在父授予授予中概述的特定目的的实现，并提高研究计划的整体节奏。我们建议使用噬菌体展示技术选择候选抑制剂；使用合成和天然胰凝乳蛋白酶C底物表征这些抑制剂，并通过将胰凝乳蛋白酶C的共结晶抑制剂C确定特定抑制的结构基础。公共卫生相关性：目前的赠款提案旨在开发针对人类胰凝乳蛋白酶C的新型抑制剂，该胰蛋白酶C是一种消化酶，该酶在调节其他消化酶中起着重要作用，并且与慢性胰腺炎的发展有关，这是一种经常衰弱的疾病。结果可以推动人类胰腺炎的新型诊断和治疗干预措施的发展。