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.
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