当前位置: X-MOL 学术Chem. Commun. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Fragment evolution for GPCRs: the role of secondary binding sites in optimization
Chemical Communications ( IF 4.3 ) Pub Date : 2021-09-10 , DOI: 10.1039/d1cc04636e
Florent Chevillard 1 , Ádám Kelemen 2 , Jillian G Baker 3 , Vivien A Aranyodi 2 , Frank Balzer 1 , Peter Kolb 1 , György M Keserű 2
Affiliation  

We developed a docking-based fragment evolution approach that extends orthosteric fragments towards a less conserved secondary binding pocket of GPCRs. Evaluating 13 000 extensions for the β1- and β2-adrenergic receptors we synthesized and tested 112 bitopic molecules. Our results confirmed the positive contribution of the secondary binding pocket to both potency and selectivity optimizations.

中文翻译:

GPCR 的片段进化:二级结合位点在优化中的作用

我们开发了一种基于对接的片段进化方法,将正构片段扩展到不太保守的 GPCR 二级结合口袋。我们合成并测试了 112 个双位分子,评估了 13 000 次 β 1 - 和 β 2 -肾上腺素能受体的延伸。我们的结果证实了二级结合口袋对效力和选择性优化的积极贡献。
更新日期:2021-09-22
down
wechat
bug