NEUROPEPTIDES--APPROACH TO AMIDATION EFFECTORS

生物活性多肽，其功能是激素、神经递质和 神经调节剂，因此与几乎所有的细胞 函数，已知是从较大的前兆通过 各种各样的翻译后修饰。尤其是羧基 末端酰胺化是生物活性的关键结构特征 在许多生物活性多肽中。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 缩氨酸氨基单加氧酶(PAM)催化形成 甘氨酸扩展前体的α-羟基甘氨酸衍生物。 第二种酶，缩氨酸乙醇酸裂解酶(PGL)-第一 由我们实验室报道的--催化a-脱氢酶- 羟基甘氨酸降解剂，以生产最终的酰胺化产品 乙二醇酯。我们的研究项目集中在这种碳链末端。 酰胺化抑制剂、钝化剂和底物类似物，并描绘 辅助性加工在各种细胞水平的过程中的作用 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.