A chemically stable peptide agonist to neuromedin U receptor type 2
A chemically stable peptide agonist to neuromedin U receptor type 2
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化学稳定的 2 型神经调节肽 U 受体肽激动剂
DOI：
10.1016/j.bmc.2020.115454
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发表时间：
2020
影响因子：
3.5
通讯作者：
Hayashi Yoshio
中科院分区：
文献类型：
--
作者：
Takayama Kentaro;Mori Kenji;Tanaka Akiko;Sasaki Yu;Sohma Yuko;Taguchi Akihiro;Taniguchi Atsuhiko;Sakane Toshiyasu;Yamamoto Akira;Miyazato Mikiya;Minamino Naoto;Kangawa Kenji;Hayashi Yoshio
Neuromedin U(NMU)是一种通过激活NMU受体NMUR1和NMUR2而具有食欲抑制活性和其他生理活性的多肽。2014年，我们报道了第一个NMUR2选择性激动剂3-cyclohexylpropionyl-Leu-Leu-Dap-Pro-Arg-Asn-NH2(CPN-116).然而，我们发现Cpn-116在磷酸盐缓冲液中是不稳定的，这是因为nα到Nβ酰基在Dap残基上的迁移。本研究对CPN-116在不同条件下的化学稳定性进行了评价，发现其在HEPES和MES等缓冲液中相对稳定。我们还进行了构效关系研究，以获得具有更高化学稳定性的NMUR2选择性激动剂。因此，含有DAB残基的Cpn-219取代Dap成为下一代六肽NMUR2激动剂。
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 ofNα-to-Nβacyl 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.