Gly-D-Phe-His-Trp-Ala-Val-Gly-His-Leu-ψ(CH2NCHO)-Met-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: Gly-D-Phe-His-Trp-Ala-Val-Gly-His-Leu-ψ(CH2NCHO)-Met-NH2
• 英文别名: (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-phenylpropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-N-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-formylamino]-4-methylpentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-methylbutanamide
• 化学式: C₅₆H₇₈N₁₆O₁₀S
• 分子量: 1167.4
• InChiKey: AIKLPWGJFUOHKA-UCYKYQRWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  83
• 可旋转键数：
  34
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  421
• 氢给体数：
  13
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  N-(叔丁氧基羰基)-L-亮氨酸-N′-甲氧基-N′-甲酰胺 在 lithium aluminium tetrahydride 作用下， 生成 Gly-D-Phe-His-Trp-Ala-Val-Gly-His-Leu-ψ(CH2NCHO)-Met-NH2
  参考文献：
  名称：

  Synthesis and biological evaluation of novel potent antagonists of the bombesin/gastrin releasing peptide receptor

  摘要：

  This paper reports the synthesis and antagonist activity of 20 C-terminal analogues of gastrin releasing peptide (GRP). The ability of each analogue to inhibit bombesin (BN) stimulated amylase release from rat pancreatic acini was determined, and those showing antagonist activity were further evaluated for their ability to inhibit BN-stimulated [H-3]thymidine uptake in serum-starved 3T3 cells. The assays also included two known peptide antagonists, C (Leu14,psi13,14]BN) and H (N-pivaloyl-GRP20-25-(R)-2-methyl-4-nonylamide) as positive controls. On the basis of these assays we suggest that a des-Met27,Leu26-psi[CH2NHCOCH3]GRP C-terminal octapeptide imparts antagonist activity. The two most active compounds are peptides 14 ([D-Phe19,Leu26-psi(CH2NHCOCH3)]GRP19-26 and 18 ([D-Phe19,Gln20,Leu26-psi(CH2NHCOCH3)]GRP19-26). In their ability to inhibit BN-stimulated [H-3]thymidine uptake, the IC50 of peptides C, H, 14, and 18 were 43.2, 31.2, 2.7, and 32.5 nM, respectively. In conclusion, the novel C-terminal psi[CH2NHCOCH3] bond promises to be a useful peptide backbone modification for imparting antagonism in GRP/BN analogues.

  DOI：

  10.1021/jm00103a007

文献信息

• Synthesis and biological evaluation of novel potent antagonists of the bombesin/gastrin releasing peptide receptor
  作者：Michael Mokotoff、Kaijun Ren、Lan K. Wong、Ann V. LeFever、Ping C. Lee

  DOI：10.1021/jm00103a007

  日期：1992.12

  This paper reports the synthesis and antagonist activity of 20 C-terminal analogues of gastrin releasing peptide (GRP). The ability of each analogue to inhibit bombesin (BN) stimulated amylase release from rat pancreatic acini was determined, and those showing antagonist activity were further evaluated for their ability to inhibit BN-stimulated [H-3]thymidine uptake in serum-starved 3T3 cells. The assays also included two known peptide antagonists, C (Leu14,psi13,14]BN) and H (N-pivaloyl-GRP20-25-(R)-2-methyl-4-nonylamide) as positive controls. On the basis of these assays we suggest that a des-Met27,Leu26-psi[CH2NHCOCH3]GRP C-terminal octapeptide imparts antagonist activity. The two most active compounds are peptides 14 ([D-Phe19,Leu26-psi(CH2NHCOCH3)]GRP19-26 and 18 ([D-Phe19,Gln20,Leu26-psi(CH2NHCOCH3)]GRP19-26). In their ability to inhibit BN-stimulated [H-3]thymidine uptake, the IC50 of peptides C, H, 14, and 18 were 43.2, 31.2, 2.7, and 32.5 nM, respectively. In conclusion, the novel C-terminal psi[CH2NHCOCH3] bond promises to be a useful peptide backbone modification for imparting antagonism in GRP/BN analogues.