脯氨酰内肽酶检测方法及抑制剂构效关系研究

Research in assays for prolyl endopeptidase activity and structure-activity relationship of its inhibitors

脯氨酰内肽酶(prolyl endopeptidase,PREP)是一种重要的丝氨酸蛋白水解酶,特异性水解多肽链中脯氨酸羧基端的肽键,参与神经肽的代谢调节,其活性与多种精神类疾病的发生发展密切相关。人体内PREP活性异常可能是阿尔茨海默病易感性的标志。总结PREP活性检测方法及其抑制剂的研究进展:检测方法方面,生化分析方法主要包括探针底物及其分析条件和动力学参数;抑制剂方面,根据来源和结构骨架分类归纳,包括黄酮类、生物碱类、萜类、菲醌类、脯氨酸类、硼酸类、噻唑类和其他类;通过进一步探讨PREP抑制剂的构效关系,以期为PREP抑制剂的高通量筛选及研发提供参考。

Prolyl endopeptidase(PREP), as an important serine protease,can specially hydrolyze the proline-containing peptides at the carboxyl terminus,and participate in the metabolism regulation of neuropeptide.Its activity shows the tight correlation with occurrence and development of mental diseases. Altered PREP activity in human may be a sign for susceptibility to Alzheimer’s disease. This paper reviews the research advances in determination methods for PREP activity and development of enzyme inhibitors.In detection methods, biochemical analysis including probe substrates, analysis conditions and pharmacokinetic parameters are introduced. PREP inhibitors include flavonoids, alkaloids, terpenes, phenanthrenequinone, proline, boric acid, thiazole and others, which are classified based on sources and chemical structures,and the structure-activity relationships are further discussed. It might provide references for high-throughput screening and development of PREP inhibitors.