以S-腺苷同型半胱氨酸水解酶为潜在靶点的新药研究进展

Advances in research of novel drugs based on S-adenosyl-L-homocysteine hydrolase as a potential target

S-腺苷同型半胱氨酸水解酶(SAHH)是细胞内广泛存在的一种酶,它催化S-腺苷同型半胱氨酸(AdoHcy)水解生成腺苷和同型半胱氨酸。抑制SAHH将导致细胞内甲基化抑制物AdoHcy的堆积,从而对转甲基反应产生反馈性抑制作用。而甲基化对于维持细胞的活性是必需的。鉴于SAHH在调节生物体转甲基化反应中的核心地位,它已被选择作为多种新药研发的重要靶点,包括免疫抑制剂、抗病毒药、防治动脉粥样硬化和阿尔茨海默病药物。SAHH抑制剂全新的化学结构、良好的作用效果和独特的作用靶点已引起国内外研究者广泛的兴趣。

S-Adenosyl-L-homocysteine hydrolase （SAHH） is a ubiquitous enzyme catalyzing the hydrolysis of S-adenosyl-L-homocysteine （AdoHcy） to adenosine and homocysteine in mammalian cells. Inhibition of SAHH has been known to result in accumulation of intracellular levels of AdoHcy, which is a potent inhibitor of all S-adenosyl-L-methionine-dependent transmethylation reactions. Based on the observation that mammalian cells appear to be dependent on methylation for activation, SAHH has recently been selected as an attractive specific target for design of agents for immunosuppression, antiviral, treatment of atherosclerosis and Alzheimer＇s disease. More and more research-ers have focused their attention on SAHH inhibitors because of the original chemistry structure, potent efficacy, and unique mechanisms.