Lagoutte Roman, Winssinger Nicolas
Faculty of Science, Department of Organic Chemistry NCCR Chemical Biology University of Geneva 30 quai Ernest Ansermet, CH-1205 Geneva.
Faculty of Science, Department of Organic Chemistry NCCR Chemical Biology University of Geneva 30 quai Ernest Ansermet, CH-1205 Geneva;, Email:
Chimia (Aarau). 2017 Oct 25;71(10):703-711. doi: 10.2533/chimia.2017.703.
Covalent inhibitors are re-emerging as pharmacologically interesting entities with several candidates having received recent approval for therapeutic intervention. Nature has embraced this strategy and many natural products possess mildly electrophilic moieties able to covalently engage a target protein. This review surveys recent case studies for the identification of the target proteins of natural products. While sesquiterpene lactones represent a vast repertoire of covalent inhibitors, they can also be found in other classes of natural products, with sometimes unusual mechanisms to unmask the electrophilic moieties. These examples ought to be inspiring for the development of new biochemical probes and tomorrow's first-in-class drugs.
共价抑制剂作为具有药理学意义的实体正在重新兴起，已有几种候选药物最近获得了治疗干预的批准。自然界也采用了这种策略，许多天然产物含有能够与靶蛋白共价结合的轻度亲电部分。这篇综述调查了最近用于鉴定天然产物靶蛋白的案例研究。虽然倍半萜内酯是共价抑制剂的一个庞大类别，但它们也可以在其他类别的天然产物中找到，有时具有揭示亲电部分的不同寻常机制。这些例子应该会激发新型生化探针和明日同类首创药物的开发。
