Ac-Nle-c[Asp-cis-4-guanidinyl-Pro-DPhe-Arg-Trp-Lys]-NH2 | 1155867-01-8

• 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: Ac-Nle-c[Asp-cis-4-guanidinyl-Pro-DPhe-Arg-Trp-Lys]-NH2
• 英文别名: (3S,11S,14S,17S,20R,23S,25S)-3-[[(2S)-2-acetamidohexanoyl]amino]-20-benzyl-25-(diaminomethylideneamino)-17-[3-(diaminomethylideneamino)propyl]-14-(1H-indol-3-ylmethyl)-2,5,13,16,19,22-hexaoxo-1,6,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide
• CAS: 1155867-01-8
• 化学式: C₅₀H₇₂N₁₆O₉
• 分子量: 1041.22
• InChiKey: UMHVNRYGRKBTCG-KARZDNGNSA-N

物化性质

• 密度：
  1.47±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  75
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  412
• 氢给体数：
  13
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  乙酸酐 、 Fmoc-D-苯丙氨酸 、 芴甲氧羰酰基正亮氨酸 、 N-[(9H-芴-9-甲氧基)羰基]-N'-[(2-丙烯氧基)羰基]-L-赖氨酸 、 Fmoc-L-天冬氨酸 4-烯丙酯 、 Fmoc-L-色氨酸(Boc)-OH 、 Fmoc-Pbf-L-精氨酸 、 (2S,4S)-N^α-Fmoc-4-N,N'-di-Boc-guanidinoproline 在 6-氯-1-羟基苯并三氮唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 Ac-Nle-c[Asp-cis-4-guanidinyl-Pro-DPhe-Arg-Trp-Lys]-NH2
  参考文献：
  名称：

  Substitution of Arginine with Proline and Proline Derivatives in Melanocyte-Stimulating Hormones Leads to Selectivity for Human Melanocortin 4 Receptor

  摘要：

  A new series of melanotropin analogues with His or Arg residues in the core pharmacophores of MTII, SHU9119, and Ac-NDP-gamma-MSH-NH2 replaced by Pro or trans-/cis-4-guanidinyl-Pro derivatives were designed and synthesized to introduce selectivity toward the human melanocortin 4 receptor (hMC4R). Analogues 1,. 2, 3, 6, 7, 8 were found to be hMC4R selective. Second messenger studies have demonstrated that analogues 1 and 2 are insurmountable inhibitors of MTII agonist activity at the hMC4R. Molecular modeling studies suggest that the hMC4R selectivity is due to a beta-turn shift induced by the Pro ring that makes the global minimum structures of these analogues resemble the NMR solution. structure of the hASIP melanocortin receptor binding motif. Substitution of His in MTII also provided functional selectivity for the hMC3R or the hMC4R. These findings are important for a better understanding of the selectivity mechanism at the hMC3R/hMC4R and the development of therapeutic ligands selectively targeting the hMC4R.

  DOI：

  10.1021/jm801300c

文献信息

• Substitution of Arginine with Proline and Proline Derivatives in Melanocyte-Stimulating Hormones Leads to Selectivity for Human Melanocortin 4 Receptor
  作者：Hongchang Qu、Minying Cai、Alexander V. Mayorov、Paolo Grieco、Morgan Zingsheim、Dev Trivedi、Victor J. Hruby

  DOI：10.1021/jm801300c

  日期：2009.6.25

  A new series of melanotropin analogues with His or Arg residues in the core pharmacophores of MTII, SHU9119, and Ac-NDP-gamma-MSH-NH2 replaced by Pro or trans-/cis-4-guanidinyl-Pro derivatives were designed and synthesized to introduce selectivity toward the human melanocortin 4 receptor (hMC4R). Analogues 1,. 2, 3, 6, 7, 8 were found to be hMC4R selective. Second messenger studies have demonstrated that analogues 1 and 2 are insurmountable inhibitors of MTII agonist activity at the hMC4R. Molecular modeling studies suggest that the hMC4R selectivity is due to a beta-turn shift induced by the Pro ring that makes the global minimum structures of these analogues resemble the NMR solution. structure of the hASIP melanocortin receptor binding motif. Substitution of His in MTII also provided functional selectivity for the hMC3R or the hMC4R. These findings are important for a better understanding of the selectivity mechanism at the hMC3R/hMC4R and the development of therapeutic ligands selectively targeting the hMC4R.