3,3,3-triphenylpropionyl-His-D-Phe-Arg-Trp-NH2

• 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: 3,3,3-triphenylpropionyl-His-D-Phe-Arg-Trp-NH2
• 英文别名: (2S)-N-[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-[[(2R)-2-[[(2S)-3-(1H-imidazol-5-yl)-2-(3,3,3-triphenylpropanoylamino)propanoyl]amino]-3-phenylpropanoyl]amino]pentanamide
• 化学式: C₅₃H₅₇N₁₁O₅
• 分子量: 928.106
• InChiKey: QDXRKEIPWRZRTH-XNTJGGFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  69
• 可旋转键数：
  23
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  268
• 氢给体数：
  9
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,3,3-三苯基丙酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 哌啶 、 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 、 三异丙基硅烷 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 3.0h， 生成 3,3,3-triphenylpropionyl-His-D-Phe-Arg-Trp-NH2
  参考文献：
  名称：

  Characterization of aliphatic, cyclic, and aromatic N-terminally “capped” His-d-Phe-Arg-Trp-NH2 tetrapeptides at the melanocortin receptors

  摘要：

  The melanocortin system is implicated in multiple physiological pathways including pigmentation, inflammation, erectile function, feeding behavior, energy homeostasis, weight homeostasis, and exocrine gland function, just to list a few. The endogenous agonists for the melanocortin receptors include the gene transcripts derived from the proopiomelanocortin gene and include the core tetrapeptide His-Phe-Arg-Trp sequence postulated to be important for melanocortin receptor selectivity and stimulation. Posttranslational processing of the proopiomelanocortin derived agonists results in the N-terminal acetylation and C-terminal amidation of alpha-melanocyte stimulation hormone (alpha-MSH). In this study we generated 25 N-terminally "capped" tetrapeptides containing the core sequence X-His-D-Phe-Arg-Trp-NH2 and pharmacologically characterized them at the mouse melanocortin,MC1 receptor, melanocortin MC3 receptor, melanocortin MC4 receptor, and melanocortin MC5 receptor. The N-terminal "capping" groups consisted of linear, cyclic, or aromatic moieties and all resulted in full agonist activity at the melanocortin receptors examined in this study. Increasing aliphatic chain length increased potency of the tetrapeptide derivatives, with the addition of octanoyl capping group resulting in 70- to 110-fold increased tetrapeptide potency at the melanocortin MC1 receptor (EC50=0.4 nM), melanocortin MC3 receptor (EC50=4.0 nM), and melanocortin MC4 receptor (EC50=0.4 nM) while only enhancing potency at the melanocortin MC5 receptor (EC50 = 0. 8 nM) by 8-fold, compared to the tetrapeptide HiS-D-Phe-Arg-Trp-NH2. This octanoyl derivative surprisingly resulted in a 14-fold greater potency than alpha-MSH (EC50 = 5.4 nM) at the mouse melanocortin MC4 receptor implicated in feeding behavior and obesity. The 3,3,3-triphenylpropionyl derivative resulted in greater than 14 muM agonist potencies at the melanocortin MC1 receptor, melanocortin MC3 receptor, and melanocortin MC4 receptor and possessed a 140 nM agonist EC50 value at the melanocortin MC5 receptor. This 3,3,3-triphenylpropionyl-His-D-Phe-Arg-Trp-NH2 peptide is a 100-fold selective agonist for the melanocortin MC5 receptor, versus the other melanocortin receptors studied herein, and is the first melanocortin MC5 receptor selective tetrapeptide derivative reported to date with nanomolar potency. (C) 2003 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0014-2999(03)01322-0