人工合成非肽类Caspase-3抑制剂的研究进展

Research Process on Artificial Synthesis of Non-peptidic Inhibitors of Caspase-3

半胱氨酸蛋白酶(Caspase)家族是代表着一类细胞内的蛋白酶系统,在介导细胞凋亡扮演着重要的角色[1].细胞凋亡的发生是一个复杂Caspase家族引导的蛋白酶级联反应过程,尽管对于不同的细胞或不同信号传导途径诱发的凋亡过程中参与的Caspase有所不同,但Caspase-3是细胞凋亡蛋白酶级联反应的必经之路,也是凋亡的关键酶和执行者.而由Caspase调控的细胞凋亡的不正常激活是引起人体机能紊乱的一些疾病的主要根源,例如肿瘤、自身免疫性疾病、病毒性感染以及各种神经退行性疾病等.所以针对Caspases-3的抑制剂将可能是上述疾病的一种非常有效的治疗药物.由于天然的Caspase抑制剂和人工合成肽类Caspase抑制剂在特异性,透膜性,体内稳定性和活性等方面的不足,人们便开始了对人工合成非肽类抑制剂的研究.本文对近年来人工合成非肽类Caspase-3抑制剂的研究进展情况作一综述.

Caspase, a unique family of cysteine proteases, is a cellular protease system, which plays an important role in mediating cell apoptosis. The occurring of cell apoptosis is a complex protease cascade reaction process induced by caspase family proteins. Although there are different caspase proteins which participate in the different celluar or signal transduction pathways, caspase-3 is the essential component in the protease cascade reaction processes of cell apoptosis and the crucial enzyme and executive of apoptosis. The abnormal activation of cell apoptosis regulated by caspase proteins is the major origin of human functional disordfer, such as tumor, autoimmune disese, virus infection and various neural degenerative diseases et al. So the inhibitor of caspase-3 will be a potential effective drug for the treatment of diseases mentioned above. Considering the insufficiency of natural and synthetic peptide caspase inhibitors in specificity, membrane-permeability, in vivo stability and activity, people commence the researches about the synthetic non-peptide caspase-3 inhibitor. The review is focus on the recent progresses on the researches of the synthetic non-peptides caspase- 3 inhibitor.