酶过渡态与药物设计。
Enzymatic Transition States and Drug Design.
机构信息
Department of Biochemistry , Albert Einstein College of Medicine , 1300 Morris Park Avenue , Bronx , New York 10461 , United States.
出版信息
Chem Rev. 2018 Nov 28;118(22):11194-11258. doi: 10.1021/acs.chemrev.8b00369. Epub 2018 Oct 18.
Abstract
Transition state theory teaches that chemically stable mimics of enzymatic transition states will bind tightly to their cognate enzymes. Kinetic isotope effects combined with computational quantum chemistry provides enzymatic transition state information with sufficient fidelity to design transition state analogues. Examples are selected from various stages of drug development to demonstrate the application of transition state theory, inhibitor design, physicochemical characterization of transition state analogues, and their progress in drug development.
摘要
过渡态理论告诉我们，化学稳定的酶过渡态类似物将紧密结合其同源酶。动力学同位素效应与计算量子化学相结合，为设计过渡态类似物提供了具有足够保真度的酶过渡态信息。本文从药物开发的各个阶段选择了一些例子，以展示过渡态理论、抑制剂设计、过渡态类似物的物理化学特性及其在药物开发中的进展的应用。
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