(S)-3-[2-({(S)-2-[(S)-2-((S)-2-{(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-4-methylsulfanyl-butylamino}-3-phenyl-propionylamino)-3-(3H-imidazol-4-yl)-propionylamino]-3,3-dimethyl-butyryl}-butyl-amino)-acetylamino]-succinamic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (S)-3-[2-({(S)-2-[(S)-2-((S)-2-{(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-4-methylsulfanyl-butylamino}-3-phenyl-propionylamino)-3-(3H-imidazol-4-yl)-propionylamino]-3,3-dimethyl-butyryl}-butyl-amino)-acetylamino]-succinamic acid
• 英文别名: (3S)-4-amino-3-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylsulfanylbutyl]amino]-3-phenylpropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3,3-dimethylbutanoyl]-butylamino]acetyl]amino]-4-oxobutanoic acid
• 化学式: C₄₅H₆₆N₁₀O₉S
• 分子量: 923.147
• InChiKey: VQPBAEWLRPNFDR-XJLBYMFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  65
• 可旋转键数：
  29
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  329
• 氢给体数：
  10
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 、 Boc-L-天冬氨酸 4-苄酯 、 Fmoc-NNle-OH 、 N-叔丁氧羰基-N(咪唑)-(4-甲基苯磺酰基)-L-组氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 (S)-3-[2-({(S)-2-[(S)-2-((S)-2-{(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-4-methylsulfanyl-butylamino}-3-phenyl-propionylamino)-3-(3H-imidazol-4-yl)-propionylamino]-3,3-dimethyl-butyryl}-butyl-amino)-acetylamino]-succinamic acid
  参考文献：
  名称：

  Novel Deltorphin Heptapeptide Analogs with Potent .delta. Agonist, .delta. Antagonist, or Mixed .mu. Antagonist/.delta. Agonist Properties

  摘要：

  A series of deltorphin (DLT: Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) analogs in which Leu(5) and/or Met(6) were mainly replaced by t-Leu(Tle) and/or N-alpha-alkylated glycine were synthesized and examined for their receptor binding properties and in vitro bioactivities by guinea pig ileum (GPI) and mouse vas deferens (MVD) assays. [Tle(5)]DLT(2) showed a dramatic decrease in the MVD potency when compared to the parent peptide and was found to have a potent delta receptor antagonist activity against various delta agonists with K-e values of 16-311 nM. Interestingly, the antagonist potency of 2 against DPDPE as agonist was 20-fold weaker than that against deltorphins or Leu-enkephalin. Among the analogs in which Met(6) was replaced by an N-alpha-alkylated Gly residue, [N-alpha-isobutyl-Gly(6)]DLT(5) behaved as a mixed mu antagonist/delta agonist while its isomeric analogs in which the N-alpha-alkyl is n-butyl (4) or (R or S) sec-butyl (6a,b) were very potent delta receptor agonists. Analogs 2, 4, 6a, and 6b were highly stable against rat brain and rat plasma enzymes and thus may represent a starting point for the development of novel receptor-specific compounds useful as ligands for studies of opioid receptors.

  DOI：

  10.1021/jm00020a013

文献信息

• Novel Deltorphin Heptapeptide Analogs with Potent .delta. Agonist, .delta. Antagonist, or Mixed .mu. Antagonist/.delta. Agonist Properties
  作者：Yusuke Sasaki、Takako Chiba

  DOI：10.1021/jm00020a013

  日期：1995.9

  A series of deltorphin (DLT: Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) analogs in which Leu(5) and/or Met(6) were mainly replaced by t-Leu(Tle) and/or N-alpha-alkylated glycine were synthesized and examined for their receptor binding properties and in vitro bioactivities by guinea pig ileum (GPI) and mouse vas deferens (MVD) assays. [Tle(5)]DLT(2) showed a dramatic decrease in the MVD potency when compared to the parent peptide and was found to have a potent delta receptor antagonist activity against various delta agonists with K-e values of 16-311 nM. Interestingly, the antagonist potency of 2 against DPDPE as agonist was 20-fold weaker than that against deltorphins or Leu-enkephalin. Among the analogs in which Met(6) was replaced by an N-alpha-alkylated Gly residue, [N-alpha-isobutyl-Gly(6)]DLT(5) behaved as a mixed mu antagonist/delta agonist while its isomeric analogs in which the N-alpha-alkyl is n-butyl (4) or (R or S) sec-butyl (6a,b) were very potent delta receptor agonists. Analogs 2, 4, 6a, and 6b were highly stable against rat brain and rat plasma enzymes and thus may represent a starting point for the development of novel receptor-specific compounds useful as ligands for studies of opioid receptors.