Graduate School of Science and Technology, Shizuoka University, 3-5-1 Johoku, Hamamatsu, Shizuoka, 432-8561, Japan.
Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University, Shizuoka 432-8561, Japan.
Chem Commun (Camb). 2024 Mar 26;60(26):3563-3566. doi: 10.1039/d3cc06197c.
CPN-116 is a peptidic agonist that activates human neuromedin U receptor type 2 (NMUR2) but suffers from chemical instability due to inherent backbone isomerization on the Dap residue. To address this, a Leu-Dap-type ()-chloroalkene dipeptide isostere was synthesized diastereoselectively as a surrogate of the Leu-Dap peptide bond to develop a ()-chloroalkene analogue of CPN-116. The synthesized CPN-116 analogue is stable in 1.0 M phosphate buffer (pH 7.4) without backbone isomerization and can activate NMUR2 with similar potency to CPN-116 at nM concentrations (EC = 1.0 nM).
CPN-116 是一种肽类激动剂，能激活人类神经肽 U 受体 2 型（NMUR2），但由于 Dap 残基上的固有骨架异构化，其化学稳定性较差。为了解决这个问题，合成了立体选择性的 Leu-Dap 型（）-氯代烯二肽作为 Leu-Dap 肽键的替代物，以开发 CPN-116 的（）-氯代烯类似物。合成的 CPN-116 类似物在 1.0 M 磷酸盐缓冲液（pH 7.4）中没有骨架异构化，并且可以在 nM 浓度下以与 CPN-116 相似的效力激活 NMUR2（EC = 1.0 nM）。
