N-acetylated human neuromedin U (AA 19 - 25) | 1393656-63-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-acetylated human neuromedin U (AA 19 - 25)
• 英文别名: Ac-FLFRPRN
• CAS: 1393656-63-7
• 化学式: C₄₇H₇₀N₁₄O₁₀
• 分子量: 991.161
• InChiKey: KXZWPHMRUXTYBU-PEAOEFARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.08
• 重原子数：
  71.0
• 可旋转键数：
  29.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  399.1
• 氢给体数：
  14.0
• 氢受体数：
  11.0

反应信息

• 作为产物：
  描述：

  Fmoc-L-亮氨酸 、 Fmoc-L-脯氨酸 、 Fmoc-L-苯丙氨酸 、 乙酸酐 、 Fmoc-N-三苯甲基-L-天冬酰胺 、 Fmoc-Pbf-L-精氨酸 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-acetylated human neuromedin U (AA 19 - 25)
  参考文献：
  名称：

  PEGylation of Neuromedin U yields a promising candidate for the treatment of obesity and diabetes

  摘要：

  Neuromedin U (NMU) is an endogenous peptide, whose role in the regulation of feeding and energy homeostasis is well documented. Two NMU receptors have been identified: NMUR1, expressed primarily in the periphery, and NMUR2, expressed predominantly in the brain. We recently demonstrated that acute peripheral administration of NMU exerts potent but acute anorectic activity and can improve glucose homeostasis, with both actions mediated by NMUR1. Here, we describe the development of a metabolically stable analog of NMU, based on derivatization of the native peptide with high molecular weight poly(ethylene) glycol (PEG) ('PEGylation'). PEG size, site of attachment, and conjugation chemistry were optimized, to yield an analog which displays robust and long-lasting anorectic activity and significant glucose-lowering activity in vivo. Studies in NMU receptor-deficient mice showed that PEG-NMU displays an expanded pharmacological profile, with the ability to engage NMUR2 in addition to NMUR1. In light of these data, PEGylated derivatives of NMU represent promising candidates for the treatment of obesity and diabetes. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.003