嘌呤补救的过渡态抑制剂和疟疾中的其他潜在酶靶标。
Transition-state inhibitors of purine salvage and other prospective enzyme targets in malaria.
机构信息
Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
出版信息
Future Med Chem. 2013 Jul;5(11):1341-60. doi: 10.4155/fmc.13.51.
Abstract
Malaria is a leading cause of human death within the tropics. The gradual generation of drug resistance imposes an urgent need for the development of new and selective antimalarial agents. Kinetic isotope effects coupled to computational chemistry have provided the relevant details on geometry and charge of enzymatic transition states to facilitate the design of transition-state analogs. These features have been reproduced into chemically stable mimics through synthetic chemistry, generating inhibitors with dissociation constants in the pico- to femto-molar range. Transition-state analogs are expected to contribute to the control of malaria.
摘要
疟疾是热带地区人类死亡的主要原因。药物逐渐产生耐药性，迫切需要开发新的、有选择性的抗疟药物。动力学同位素效应与计算化学相结合，为酶促过渡态的几何形状和电荷提供了相关细节，从而有助于过渡态类似物的设计。这些特征已通过合成化学复制到化学稳定的模拟物中，产生的抑制剂的离解常数在皮摩尔到飞摩尔范围内。过渡态类似物有望有助于控制疟疾。
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