Powers J C, Odake S, Oleksyszyn J, Hori H, Ueda T, Boduszek B, Kam C
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta 30332.
Agents Actions Suppl. 1993;42:3-18.
Proteases have been divided into four mechanistic classes: serine proteases, metalloproteases, aspartic proteases, and cysteine proteases. Once a new enzyme is classified by the use of general inhibitors, it is possible to design reactive inhibitors by using mechanistic information learned through study of other members of the same protease family. The most useful types of inhibitors for serine proteases are transition-state inhibitors including alpha-ketoesters and phosphonates, and mechanism-based inhibitors such as heterocyclic isocoumarin inhibitors. Some of these inhibitors are quite specific toward individual target serine proteases. Many proteases are involved in various disease states, and potent inhibitors of these enzymes have the potential to be developed as new therapeutic agents. In the future, it is likely than numberous specific protease inhibitors will be tested clinically for the treatment of human disease.
丝氨酸蛋白酶、金属蛋白酶、天冬氨酸蛋白酶和半胱氨酸蛋白酶。一旦通过使用通用抑制剂对一种新酶进行分类，就有可能利用通过研究同一蛋白酶家族的其他成员所获得的机制信息来设计活性抑制剂。对丝氨酸蛋白酶最有用的抑制剂类型是过渡态抑制剂，包括α-酮酯和膦酸酯，以及基于机制的抑制剂，如杂环异香豆素抑制剂。其中一些抑制剂对个别目标丝氨酸蛋白酶具有相当的特异性。许多蛋白酶与各种疾病状态有关，这些酶的强效抑制剂有潜力被开发为新的治疗药物。未来，可能会有大量特异性蛋白酶抑制剂用于人类疾病治疗的临床测试。
