von Itzstein M, Dyason J C, Oliver S W, White H F, Wu W Y, Kok G B, Pegg M S
Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, Parkville, Australia.
J Med Chem. 1996 Jan 19;39(2):388-91. doi: 10.1021/jm950294c.
The development of sialidase inhibitor-based potential anti-influenza drugs using rational drug design techniques has been of recent interest. The present study details as investigation of the active site of influenza virus sialidase by using the program GRID in an attempt to design more potent inhibitors in the hope they will eventually lead to anti-influenza drugs. A number of different probes (amino, carboxy, hydroxy, methyl, etc) have been used in an effort to determine the functional groups most likely to improve the binding of the starting template 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en). The data have correctly predicted the binding regions for the carboxylate, acetamido (NH and methyl), and glycerol (OH) groups of N-acetylneuraminic acid. Moreover, the data suggest that the addition of certain functionalities (amino group) at the C-4 position should enhance the overall binding.
利用合理药物设计技术开发基于唾液酸酶抑制剂的潜在抗流感药物近来备受关注。本研究详细阐述了通过使用GRID程序对流感病毒唾液酸酶活性位点进行的研究，旨在设计更有效的抑制剂，期望它们最终能成为抗流感药物。为了确定最有可能改善起始模板2-脱氧-2,3-二脱氢-N-乙酰神经氨酸（Neu5Ac2en）结合的官能团，已使用了多种不同的探针（氨基、羧基、羟基、甲基等）。数据正确预测了N-乙酰神经氨酸的羧酸盐、乙酰氨基（NH和甲基）以及甘油（OH）基团的结合区域。此外，数据表明在C-4位置添加某些官能团（氨基）应能增强整体结合。
