基于机制的酪氨酸氨基变位酶SgTAM抑制剂的设计与表征
Design and characterization of mechanism-based inhibitors for the tyrosine aminomutase SgTAM.
作者信息
Montavon Timothy J, Christianson Carl V, Festin Grace M, Shen Ben, Bruner Steven D
机构信息
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA.
出版信息
Bioorg Med Chem Lett. 2008 May 15;18(10):3099-102. doi: 10.1016/j.bmcl.2007.11.046. Epub 2007 Nov 19.
Abstract
The synthesis and evaluation of two classes of inhibitors for SgTAM, a 4-methylideneimidazole-5-one (MIO) containing tyrosine aminomutase, are described. A mechanism-based strategy was used to design analogs that mimic the substrate or product of the reaction and form covalent interactions with the enzyme through the MIO prosthetic group. The analogs were characterized by measuring inhibition constants and X-ray crystallographic structural analysis of the co-complexes bound to the aminomutase, SgTAM.
摘要
本文描述了两类针对SgTAM（一种含4-亚甲基咪唑-5-酮（MIO）的酪氨酸氨基变位酶）抑制剂的合成与评估。采用基于机制的策略设计类似物，这些类似物模拟反应的底物或产物，并通过MIO辅基与酶形成共价相互作用。通过测量抑制常数以及对与氨基变位酶SgTAM结合的共复合物进行X射线晶体学结构分析，对这些类似物进行了表征。
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