作为针对 EP2 的有前途配体，环状 γ-AApeptides 的发现。

The discovery of cyclic γ-AApeptides as the promising ligands targeting EP2.

机构信息

Department of Chemistry, University of South Florida, 4202 E. Fowler Ave, Tampa, FL 33620, USA.

Department of Pharmaceutical Sciences, Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

出版信息

Bioorg Med Chem Lett. 2023 May 1;87:129255. doi: 10.1016/j.bmcl.2023.129255. Epub 2023 Mar 23.

DOI:10.1016/j.bmcl.2023.129255

PMID:36965536

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10141659/

Abstract

EP2 is a G protein-coupled receptor for prostaglandin E2 (PGE2) derived from cell membrane-released arachidonic acid upon various harmful and injurious stimuli. It is commomly upregulated in tumors and injured brain tissues, as its activation by PGE2 is widely believed to be involved in the pathophysiological mechanisms underlying these conditions via promoting pro-inflammatory reactions. Herein, we report the discovery of two novel macrocyclic peptidomimetics based on the screening of a cyclic γ-AApeptides combinatorial library. These two cyclic γ-AApeptides showed excellent binding affinity with the EP2 protein, and they may lead to the development of novel therapeutic agents and/or molecular probes to modulate the PGE2/EP2 signaling.

摘要

EP2 是前列腺素 E2（PGE2）的 G 蛋白偶联受体，由各种有害和损伤性刺激引起的细胞膜释放的花生四烯酸衍生而来。它在肿瘤和受损脑组织中通常被上调，因为其通过 PGE2 的激活被广泛认为参与了这些疾病的病理生理机制，通过促进促炎反应。在此，我们报告了两种新型的大环肽模拟物的发现，这些模拟物是基于对环状γ-AApeptides 组合文库的筛选。这两种环状γ-AApeptides 与 EP2 蛋白具有优异的结合亲和力，它们可能会导致新型治疗剂和/或分子探针的开发，以调节 PGE2/EP2 信号。