Ac-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2 | 77714-20-6

• 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-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2
• 英文别名: (2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]acetyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-4-methylpentanamide
• CAS: 77714-20-6
• 化学式: C₄₆H₆₆N₁₄O₉S
• 分子量: 991.184
• InChiKey: PESSCGOLEUORDO-IFIOYJEKSA-N

物化性质

• 沸点：
  1567.6±65.0 °C(Predicted)
• 密度：
  1.304±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  70
• 可旋转键数：
  28
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  374
• 氢给体数：
  12
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  BOC-甘氨酸 、 BOC-L-亮氨酸 、 Boc-L-蛋氨酸 、 N-[(1,1-dimethylethoxy)carbonyl]-3-[(phenylmethoxy)methyl]-L-histidine 、 alkaline earth salt of/the/ methylsulfuric acid 生成 Ac-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2
  参考文献：
  名称：

  Gastrin releasing peptide antagonists with improved potency and stability

  摘要：

  Gastrin releasing peptide (GRP) is a 27 amino acid peptide hormone which is homologous to the amphibian peptide bombesin. Two series of novel GRP antagonists were developed by C-terminal modification of N-acetyl-GRP-20-27 amide. Peptide derivatives within each series resist enzymatic degradation in serum and exhibit strong affinity for the GRP receptor. The first series of compounds replaces the Leu26-Met27 region of GRP with an alkyl ether moiety. One member of this series, N-acetyl-GRP-20-25-NH-[(S)-1-ethoxy-4-methyl-2-pentane], specifically blocked radiolabeled GRP binding with an IC50 of 6 nM. In the second series of antagonists the oxygen of the ether moiety is replaced with a methylene group, resulting in GRP antagonists which are equipotent to native GRP in receptor binding assays (IC50 = 2 nM) and are also resistant to proteolytic degradation in vitro. All of the C-terminally modified peptides tested blocked GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts. Representative compounds also blocked GRP-induced elevation of [Ca2+]i in human SCLC cells, and inhibited GRP-independent release of gastrin in vivo.

  DOI：

  10.1021/jm00111a027

文献信息

• Gastrin releasing peptide antagonists with improved potency and stability
  作者：David C. Heimbrook、Walfred S. Saari、Nancy L. Balishin、Thorsten W. Fisher、Arthur Friedman、David M. Kiefer、Nicola S. Rotberg、John W. Wallen、Allen Oliff

  DOI：10.1021/jm00111a027

  日期：1991.7

  Gastrin releasing peptide (GRP) is a 27 amino acid peptide hormone which is homologous to the amphibian peptide bombesin. Two series of novel GRP antagonists were developed by C-terminal modification of N-acetyl-GRP-20-27 amide. Peptide derivatives within each series resist enzymatic degradation in serum and exhibit strong affinity for the GRP receptor. The first series of compounds replaces the Leu26-Met27 region of GRP with an alkyl ether moiety. One member of this series, N-acetyl-GRP-20-25-NH-[(S)-1-ethoxy-4-methyl-2-pentane], specifically blocked radiolabeled GRP binding with an IC50 of 6 nM. In the second series of antagonists the oxygen of the ether moiety is replaced with a methylene group, resulting in GRP antagonists which are equipotent to native GRP in receptor binding assays (IC50 = 2 nM) and are also resistant to proteolytic degradation in vitro. All of the C-terminally modified peptides tested blocked GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts. Representative compounds also blocked GRP-induced elevation of [Ca2+]i in human SCLC cells, and inhibited GRP-independent release of gastrin in vivo.