半胱氨酸蛋白酶拟肽抑制剂设计新进展

Recent Advances in Design of Cysteine Protease Peptide-Like Inhibitors

半胱氨酸蛋白酶包括多种酶,这些酶在广泛的生命过程中发挥作用。人类正常的半胱氨酸蛋白酶表达失调,寄生虫、病毒的半胱氨酸蛋白酶表达与多种病理情况相关。对于这类疾病,抑制半胱氨酸蛋白酶是一个可行的药物治疗策略。当前这类药物设计的目标是3种结构不同的半胱氨酸蛋白酶,即木瓜蛋白酶家族、半胱氨酸-天冬氨基特异性蛋白酶家族(caspases)和小核糖核酸病毒科半胱氨酸蛋白酶抑制剂家族。本文综述了近年来有关半胱氨酸蛋白酶抑制剂的设计思路。

The cysteine proteases are a large group of enzymes that play roles in a broad range of biological processes. However, imbalances in the normal expression of human cysteine proteases or involvement of parasitic or viral cysteine proteases are associated with a variety of pathological conditions. Inhibition of cysteine proteases represents a potential strategy for chemotherapy in such cases. Three structurally different classes of cysteine proteases are current targets for drug design： the papain family, the caspases and the picoruaviridae family.