His-D-Phe-Arg-Trp-NH2 | 308340-70-7

• 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: His-D-Phe-Arg-Trp-NH2
• 英文别名: L-Histidyl-D-phenylalanyl-N~5~-(diaminomethylidene)-L-ornithyl-L-tryptophanamide；(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)pentanamide
• CAS: 308340-70-7
• 化学式: C₃₂H₄₁N₁₁O₄
• 分子量: 643.749
• InChiKey: OVIZBCMXCJAPHP-PGXSJUQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  47
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  265
• 氢给体数：
  9
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  Fmoc-D-苯丙氨酸 、 N_α-(Fluoren-9-ylmethoxycarbonyl)-N_(im)-(tert-butyloxycarbonyl)-L-histidine 、 Fmoc-L-色氨酸(Boc)-OH 、 Fmoc-Arg(Pbf)-OH 生成 His-D-Phe-Arg-Trp-NH2
  参考文献：
  名称：

  Sub-Nanomolar hMC1R Agonists by End-Capping of the Melanocortin Tetrapeptide His-d-Phe-Arg-Trp-NH2

  摘要：

  Twenty three derivatives of the core fragment His(6)-D-Phe(7)-Arg(8)-Trp(9)-NH2 end-capped with carboxylic and sulfonic acids were synthesized and evaluated at human melanocortin receptors (hMC1, hMC3, and hMC4Rs). The SAR within this series allowed us to map the hMCRs near the His(6) binding site and design a superpotent MC1R agonist, LK-184, Ph(CH2)(3)CO-HiS-D-Phe-Arg-Trp-NH2 (19) with EC50 0.01 nM (5 nM at MC3 and MC4Rs). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00552-3

文献信息

• Melanocortin receptor ligands
  申请人：The Procter & Gamble Company

  公开号：US20030109556A1

  公开（公告）日：2003-06-12

  Disclosed are MC-3/MC-4 receptor ligands, the ligands having the following formula: 1 wherein A is a conformationally restricted ring system selected from the group consisting of: a) non-aromatic carbocyclic rings; b) aromatic carbocyclic rings; c) non-aromatic heterocyclic rings; d) aromatic heterocyclic rings; wherein said rings comprises from 5 to 8 atoms; and W is a unit which preferable comprises D-1-fluorophenyalanine, Y comprises a heteroatom, and Z comprises an aromatic carbocyclic ring. Also disclosed are pharmaceutical compositions comprising the ligands of the invention as well as methods of treating diseases mediated through MC-3/MC-4 receptors.

  本发明涉及MC-3/MC-4受体配体，该配体具有以下公式：1其中A是从以下组中选择的构象限制性环系统：a)非芳香碳环；b)芳香碳环；c)非芳香杂环；d)芳香杂环；其中所述环包含5至8个原子；W是一个单元，它更喜欢包含D-1-氟苯丙氨酸，Y包含一个杂原子，Z包含一个芳香碳环。本发明还涉及包含该配体的制药组合物，以及通过MC-3/MC-4受体介导的疾病的治疗方法。
• N-Terminal Fatty Acylated His-<scp>d</scp>Phe-Arg-Trp-NH₂ Tetrapeptides:  Influence of Fatty Acid Chain Length on Potency and Selectivity at the Mouse Melanocortin Receptors and Human Melanocytes
  作者：Aleksandar Todorovic、Jerry Ryan Holder、Rayna M. Bauzo、Joseph Walker Scott、Renny Kavanagh、Zalfa Abdel-Malek、Carrie Haskell-Luevano

  DOI：10.1021/jm0490843

  日期：2005.5.1

  The melanocortin system is involved in the regulation of a diverse number of physiologically important pathways including pigmentation, feeding behaviour, weight and energy homeostasis, inflammation, and sexual function. All the endogenous melanocortin agonist ligands possess the conserved His-Phe-Arg-Trp tetrapeptide sequence that is postulated to be important for melanocortin receptor molecular recognition and stimulation. Previous studies by our laboratory resulted in the discovery that increasing alkyl chain length at the N-terminal "capping" region of the His-DPhe-Arg-Trp-NH2 tetrapeptide resulted in a 100-fold increased melanocortin receptor agonist potency. This study was undertaken to systematically evaluate the pharmacological effects of increasing N-capping alkyl chain length of the CH3(CH2),CO-His-(D)Phe-Arg-Trp-NH2 (n = 6-16) tetrapeptide template. Twelve analogues were synthesized and pharmacologically characterized at the mouse melanocortin receptors MC1R and MC3R-MC5R and human melanocytes known to express the MC1R. These peptides demonstrated melanocortin receptor selectivity profiles different from those of previously published tetrapeptides. The most notable results of enhanced ligand potency (20- to 200-fold) and receptor selectivity were observed at the MC1R. Tetrapeptides that possessed greater than nine alkyl groups were superior to alpha-MSH in terms of the stimulation of human melanocyte tyrosinase activity. Additionally, the n-pentadecanoyl derivative had a residual effect on tyrosinase activity that existed for at least 4 days after the peptide was removed from the human melanocyte culture medium. These data demonstrate the utility, potency, and residual effect of melanocortin tetrapeptides by adding N-terminal fatty acid moieties.
• US6911447B2
  申请人：——

  公开号：US6911447B2

  公开（公告）日：2005-06-28
• US7087759B2
  申请人：——

  公开号：US7087759B2

  公开（公告）日：2006-08-08
• Sub-Nanomolar hMC1R Agonists by End-Capping of the Melanocortin Tetrapeptide His-d-Phe-Arg-Trp-NH2
  作者：L.N Koikov、F.H Ebetino、M.G Solinsky、D Cross-Doersen、J.J Knittel

  DOI：10.1016/s0960-894x(03)00552-3

  日期：2003.8

  Twenty three derivatives of the core fragment His(6)-D-Phe(7)-Arg(8)-Trp(9)-NH2 end-capped with carboxylic and sulfonic acids were synthesized and evaluated at human melanocortin receptors (hMC1, hMC3, and hMC4Rs). The SAR within this series allowed us to map the hMCRs near the His(6) binding site and design a superpotent MC1R agonist, LK-184, Ph(CH2)(3)CO-HiS-D-Phe-Arg-Trp-NH2 (19) with EC50 0.01 nM (5 nM at MC3 and MC4Rs). (C) 2003 Elsevier Ltd. All rights reserved.