Fabrice Balavoine , Delphine Compere , Frédéric Miege , Nadia De Mota , Mathilde Keck , Mickael Fer , Aude Christen , Emmeline Martin , Didier Roche , Catherine Llorens-Cortes , Vincent Rodeschini
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引用次数: 0
Abstract
Aminopeptidase A (APA) is a membrane-bound zinc metallopeptidase involved in the production of angiotensin III, one effector peptide of the brain renin-angiotensin system, making brain APA a relevant pharmacological target for the development of novel therapeutic treatments against hypertension and heart failure. The structure-based design of new APA inhibitors is described, based on previously developed thiol-containing inhibitors and APA crystal structure. Chemical synthesis, in vitro assessment against APA activity, pharmacological and pharmacokinetic profiling were performed, ultimately leading to a potent and selective APA inhibitor.
氨基肽酶 A（APA）是一种膜结合锌金属肽酶，参与脑肾素-血管紧张素系统效应肽之一血管紧张素 III 的生成，因此脑 APA 是开发高血压和心力衰竭新型疗法的相关药理学靶点。本文介绍了基于先前开发的含硫醇抑制剂和 APA 晶体结构设计的新型 APA 抑制剂。研究人员进行了化学合成、体外评估 APA 活性、药理学和药代动力学分析，最终研制出了一种强效且具有选择性的 APA 抑制剂。
期刊介绍：
Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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