NEUROPEPTIDES--APPROACH TO AMIDATION EFFECTORS

生物活性肽作为激素、神经递质和 神经调质，因此几乎参与所有细胞 函数，已知是由较大的前体通过 各种翻译后修饰。 特别地，羧基 末端酰胺化是生物活性的关键结构特征 许多生物活性肽。 现在很清楚，羧基末端 酰胺化需要两个连续的酶促步骤。 第一酶 肽酰甘氨酸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）， 据我们实验室报道--催化a- 产生最终酰胺化产物，加上 甘草酸盐 我们的研究项目集中在这个羧基末端 酰胺化抑制剂、失活剂和底物类似物， 酰胺化加工在各种细胞水平过程中的作用， 如血管功能和肿瘤细胞生长。

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.