期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 18, 页码 10247-10254出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202100180
关键词
allosteric modulators; drug discovery; fragment screening; GPCRs; peptidomimetics
资金
- Doctiris programme of Innoviris
- Strategic Research Programme of the Research Council at VUB [SRP50]
GPCRs are important membrane proteins in modern medicine. Peptidomimetics described in this study can mimic G proteins in stabilizing the active state of receptors, facilitating the discovery of agonist drugs.
G protein-coupled receptors (GPCRs) represent an important group of membrane proteins that play a central role in modern medicine. Unfortunately, conformational promiscuity hampers full therapeutic exploitation of GPCRs, since the largest population of the receptor will adopt a basal conformation, which subsequently challenges screens for agonist drug discovery programs. Herein, we describe a set of peptidomimetics able to mimic the ability of G proteins in stabilizing the active state of the beta(2) adrenergic receptor (beta(2)AR) and the dopamine 1 receptor (D1R). During fragment-based screening efforts, these (un)constrained peptide analogues of the alpha(5) helix in G(s) proteins, were able to identify agonism pre-imprinted fragments for the examined GPCRs, and as such, they behave as a generic tool, enabling an engagement in agonist earmarked discovery programs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据