Neuromedin U (NMU) is a peptide with appetite suppressive activity and other physiological activities via activation of the NMU receptors NMUR1 and NMUR2. In 2014, we reported the first NMUR2 selective agonist, 3-cyclohexylpropionyl-Leu-Leu-Dap-Pro-Arg-Asn-NH2 (CPN-116). However, we found that CPN-116 in phosphate buffer is unstable because of Nα-to-Nβ acyl migration at the Dap residue. In this study, the chemical stability of CPN-116 was evaluated under various conditions, and it was found to be relatively stable in buffers such as HEPES and MES. We also performed a structure-activity relationship study to obtain an NMUR2-selective agonist with improved chemical stability. Consequently, CPN-219 bearing a Dab residue in place of Dap emerged as a next-generation hexapeptidic NMUR2 agonist.

中文翻译：

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化学稳定的2型神经介素U受体激动剂。

Neuromedin U（NMU）是一种通过激活NMU受体NMUR1和NMUR2具有抑制食欲和其他生理活性的肽。2014年，我们报道了首个NMUR2选择性激动剂3-环己基丙酰基-Leu-Leu-Dap-Pro-Arg-Asn-NH2（CPN-116）。但是，我们发现磷酸盐缓冲液中的CPN-116不稳定，因为Dap残基上的Nα至Nβ酰基迁移。在这项研究中，对CPN-116的化学稳定性在各种条件下进行了评估，发现在缓冲液（例如HEPES和MES）中相对稳定。我们还进行了结构-活性关系研究，以获得具有改善的化学稳定性的NMUR2-选择性激动剂。因此，带有Dab残基代替Dap的CPN-219作为下一代六肽NMUR2激动剂出现。