Warner T G, Louie A, Potier M, Ribeiro A
University of Tennessee, Department of Pediatrics, Memphis 38163.
Carbohydr Res. 1991 Aug 20;215(2):315-21. doi: 10.1016/0008-6215(91)84030-i.
Kinetic analysis of mammalian sialidases was carried out using analogs of the potent sialidase inhibitor, 5-acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonic+ ++ acid (1). Substitutents at C-9 in place of the terminal hydroxyl group included a, 4-azido-2-nitrophenylthio group to give 5-acetamido-2,6-anhydro-9-S-(4-azido-2-nitrophenyl)-3,5, 9-trideoxy-9-thio-D-glycero-D-galacto-non-2-enonic acid (2), and an azide group to give 5-acetamido-2,6-anhydro-9-azido-3,5,9-trideoxy-D-glycero-D-galacto-non-2 -enonic acid (3). Competitive inhibition kinetics were observed when 1,2, and 3 were tested with the lysosomal sialidase (cultured fibroblasts) and the plasma membrane sialidase (adenovirus DNA-transformed, human embryonic kidney cells), giving a Ki of about 10 microM for both enzymes with all three compounds. In contrast, only 1 was a potent inhibitor of the microsomal sialidase (rat muscle).
使用强效唾液酸酶抑制剂5-乙酰氨基-2,6-脱水-3,5-二脱氧-D-甘油-D-半乳糖-壬-2-烯酸（1）的类似物对哺乳动物唾液酸酶进行了动力学分析。在C-9位取代末端羟基的取代基包括：a. 4-叠氮基-2-硝基苯硫基，得到5-乙酰氨基-2,6-脱水-9-S-(4-叠氮基-2-硝基苯基)-3,5,9-三脱氧-9-硫代-D-甘油-D-半乳糖-壬-2-烯酸（2）；以及一个叠氮基团，得到5-乙酰氨基-2,6-脱水-9-叠氮基-3,5,9-三脱氧-D-甘油-D-半乳糖-壬-2-烯酸（3）。当用溶酶体唾液酸酶（培养的成纤维细胞）和质膜唾液酸酶（腺病毒DNA转化的人胚肾细胞）对1、2和3进行测试时，观察到竞争性抑制动力学，这三种化合物对这两种酶的抑制常数（Ki）约为10微摩尔。相比之下，只有1是微粒体唾液酸酶（大鼠肌肉）的强效抑制剂。
