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新型抗生素的研发：Kdo8P 合酶基于机制的抑制剂的合成与评估

Towards the development of novel antibiotics: synthesis and evaluation of a mechanism-based inhibitor of Kdo8P synthase.

作者信息

Du S, Faiger H, Belakhov V, Baasov T

机构信息

Department of Chemistry and Institute of Catalysis Science and Technology, Technion-Israel Institute of Technology, Haifa.

出版信息

Bioorg Med Chem. 1999 Dec;7(12):2671-82. doi: 10.1016/s0968-0896(99)00233-3.

DOI:10.1016/s0968-0896(99)00233-3
PMID:10658571
Abstract

The design and two synthetic pathways to aminophosphonate 4 which mimics the ionic and steric properties of putative oxocarbenium intermediate 3 in the Kdo8P synthase-catalyzed reaction are reported. It was found that 4 is a slow-binding, most potent inhibitor of the enzyme yet tested, with a Ki value of 0.4 microM.

摘要

报道了氨基膦酸酯4的设计及其两条合成途径，该化合物模拟了Kdo8P合酶催化反应中假定的氧碳鎓中间体3的离子和空间性质。结果发现，4是该酶目前测试过的结合缓慢但效力最强的抑制剂，其Ki值为0.4微摩尔。

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