McConnell R M, York J L, Frizzell D, Ezell C
University of Arkansas, Monticello 71655.
J Med Chem. 1993 Apr 16;36(8):1084-9. doi: 10.1021/jm00060a016.
Fifteen tripeptide analogues of leupeptin containing either a C-terminal argininal or lysinal were synthesized. The synthetic analogues were tested, using spectrophotometric assay techniques, as inhibitors of trypsin, kallikrein, thrombin, plasmin, and cathepsin B. The lysinal analogues were fairly selective as inhibitors of cathepsin B activity. Acetyl-L-leucyl-L-valyl-L-lysinal (21) showed a stronger inhibition of cathepsin B (IC50 = 4 nanomolar) than leupeptin. Acetyl-L-phenylalanyl-L-valyl-L-argininal (2i) was found to be a good inhibitor of cathepsin B (IC50 = 0.039 microM), thrombin (IC50 = 1.8 microM), and plasmin (IC50 = 2.2 microM).
合成了十五种含有C末端精氨酸或赖氨酸的亮抑酶肽三肽类似物。使用分光光度测定技术对合成类似物作为胰蛋白酶、激肽释放酶、凝血酶、纤溶酶和组织蛋白酶B的抑制剂进行了测试。赖氨酸类似物作为组织蛋白酶B活性的抑制剂具有相当的选择性。乙酰-L-亮氨酰-L-缬氨酰-L-赖氨酸（21）对组织蛋白酶B的抑制作用（IC50 = 4纳摩尔）比亮抑酶肽更强。发现乙酰-L-苯丙氨酰-L-缬氨酰-L-精氨酸（2i）是组织蛋白酶B（IC50 = 0.039微摩尔）、凝血酶（IC50 = 1.8微摩尔）和纤溶酶（IC50 = 2.2微摩尔）的良好抑制剂。
