NEUROPEPTIDES--APPROACH TO AMIDATION EFFECTORS

神经肽--酰胺化效应物的研究方法

基本信息

批准号：
2900696
负责人：
SHELDON W MAY
金额：
$ 21.22万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-02-01 至 2002-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2900696
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

项目摘要

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，具有激素、神经递质和神经调节剂，因此几乎所有细胞都至关重要功能，已知是通过较大的前体产生的各种翻译后修饰。特别是羧基末端酰胺化是生物活性的关键结构特征多种生物活性肽。现在很清楚，羧基末端酰胺化需要两个连续的酶促步骤。第一种酶肽基甘氨酸α-酰胺化单加氧酶 (PAM) 催化形成甘氨酸延伸前体的α-羟基甘氨酸衍生物。第二种酶，肽酰氨基乙醇酸裂解酶（PGL）——第一个我们实验室报告的--催化a-的脱乙酰化- 羟基甘氨酸衍生物产生最终的酰胺化产物加上乙醛酸盐。我们的研究计划集中在这个羧基末端酰胺化抑制剂、灭活剂和底物类似物并描绘酰胺化处理在各种细胞水平过程中的作用，例如如血管功能和肿瘤细胞生长。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Reversal of the transformed phenotype and inhibition of peptidylglycine alpha-monooxygenase in Ras-transformed cells by 4-phenyl-3-butenoic acid.

4-苯基-3-丁烯酸逆转 Ras 转化细胞中的转化表型并抑制肽基甘氨酸 α-单加氧酶。

DOI：
10.1002/mc.20060
发表时间：
2004
期刊：
Molecular carcinogenesis.
影响因子：
0
作者：
Sunman,JeffreyA;Foster,MichaelS;Folse,StaceyL;May,SheldonW;Matesic,DianeF
通讯作者：
Matesic,DianeF

Pharmacological evaluation of 1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene, a novel arylacetic acid with potential anti-inflammatory properties.

1-(羧甲基)-3,5-二苯基-2-甲基苯的药理学评价，一种具有潜在抗炎特性的新型芳基乙酸。

DOI：
10.1007/s000110050335
发表时间：
1998
期刊：
Inflammation research : official journal of the European Histamine Research Society ... [et al.].
影响因子：
0
作者：
Cutler,SJ;DeWittBlantonJr,C;Akin,DT;Steinberg,FB;Moore,AB;Lott,JA;Price,TC;May,SW;Pollock,SH
通讯作者：
Pollock,SH

Reaction versus subsite stereospecificity of peptidylglycine alpha-monooxygenase and peptidylamidoglycolate lyase, the two enzymes involved in peptide amidation.

肽基甘氨酸α-单加氧酶和肽基酰胺乙醇酸裂解酶（这两种参与肽酰胺化的酶）的反应与亚位点立体特异性。