NEUROPEPTIDES--APPROACH TO AMIDATION EFFECTORS

神经肽--酰胺化效应物的研究方法

• 批准号: 2022242
• 负责人: SHELDON W MAY
• 金额: $ 24.39万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2022242
• 关键词: amidation /deamidation; carboxyl group; drug design /synthesis /production; enzyme inhibitors; enzyme substrate; enzyme substrate analog; gastrins; glycine; growth inhibitors; lyase; neoplastic growth; neuroeffector; neuropeptides; oxygenases; posttranslational modifications; tissue /cell culture; transfection; vasomotion

Bioactive peptides, which function as hormones, neurotransmitters and neuromodulators, and are thus vitally involved in virtually all cellular functions, are known to be generated from larger precursors via a variety of postranslational modifications. In particular, carboxyl terminus amidation is a key structural feature in the bioligical activity of many bioactive peptides. It is now clear that carboxyl-terminal amidation entails two sequential enzymtic steps. The first enzyme peptidylglycine a-amidating monoxygenase (PAM) catalyzes formation of the a-hydroxyglycine derivative of the glycine extended precursor. The second enzyme, peptidylamidoglycolate lyase (PGL) ---first reported by our laboratory--catalyzes dealdylation of the a- hydroxyglycine derevatives to produce the final amidated product plus glyoxylte. Our research program focuses on this carboxly-terminal amidation inhibitors, inactvator and substrate analogs and to delineate the role amidative processing in various cellular-level processes such as vascular function and tumor cell growth.

生物活性肽，作为激素，神经递质和