(tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-ψ(CH2-NH)-L-aspartyl-L-phenylalanine amide | 97530-01-3

• 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: (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-ψ(CH2-NH)-L-aspartyl-L-phenylalanine amide
• 英文别名: (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-4-methylpentyl]amino]-4-oxobutanoic acid
• CAS: 97530-01-3
• 化学式: C₃₅H₄₈N₆O₇
• 分子量: 664.802
• InChiKey: JQSNJCLXORIIKV-JSRHHAARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  48
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  205
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (tert-butyloxycarbonyl)-L-tryptophyl-L-leucine N,O-dimethylhydroxamate 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢气 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 溶剂黄146 为溶剂， 反应 5.0h， 生成 (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-ψ(CH2-NH)-L-aspartyl-L-phenylalanine amide
  参考文献：
  名称：

  Synthesis and biological activities of some pseudo-peptide analogs of tetragastrin: the importance of the peptide backbone

  摘要：

  Pseudo-peptide analogues of the C-terminal tetrapeptide of gastrin, in which a peptide bond has been replaced by a CH2-NH bond, i.e. (tert-butyloxycarbonyl)-L-tryptophyl-psi (CH2-NH)-L-leucyl-L-aspartyl-L-phenylalanine amide (8), (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-psi (CH2-NH)-L-aspartyl-L-phenylalanine amide (13), (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-L-aspartyl-psi (CH2NH)-L-phenylalanine amide (20), were synthesized. The pseudo-peptides 8 and 13 were shown to have the same affinity as (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-L-aspartyl-L-phenylalanine amide (21) for the gastrin receptor on isolated mucosal cells. The pseudo-peptide 20 exhibited lower affinity (IC50 congruent to 10(-5) M). The biological activity of these pseudo-peptides was studied on acid secretion in the anesthetized rat. Compound 8 stimulated acid secretion, identically with that of 21. Compound 13 did not exhibit any agonist activity but was able to antagonize the action of gastrin (ED50 = 0.3 mg/kg). Compound 20 did not show any agonist activity but was able to inhibit gastrin-induced acid secretion, with lower potency (ED50 = 15 mg/kg). The importance of the peptide bonds in the mode of action of gastrin is discussed, and a hypothetical approach of the mechanism of action is presented.

  DOI：

  10.1021/jm00150a020

文献信息

• Synthesis and biological activities of some pseudo-peptide analogs of tetragastrin: the importance of the peptide backbone
  作者：Jean Martinez、Jean Pierre Bali、Marc Rodriguez、B. Castro、R. Magous、Jeanine Laur、Marie Francoise Lignon

  DOI：10.1021/jm00150a020

  日期：1985.12

  Pseudo-peptide analogues of the C-terminal tetrapeptide of gastrin, in which a peptide bond has been replaced by a CH2-NH bond, i.e. (tert-butyloxycarbonyl)-L-tryptophyl-psi (CH2-NH)-L-leucyl-L-aspartyl-L-phenylalanine amide (8), (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-psi (CH2-NH)-L-aspartyl-L-phenylalanine amide (13), (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-L-aspartyl-psi (CH2NH)-L-phenylalanine amide (20), were synthesized. The pseudo-peptides 8 and 13 were shown to have the same affinity as (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-L-aspartyl-L-phenylalanine amide (21) for the gastrin receptor on isolated mucosal cells. The pseudo-peptide 20 exhibited lower affinity (IC50 congruent to 10(-5) M). The biological activity of these pseudo-peptides was studied on acid secretion in the anesthetized rat. Compound 8 stimulated acid secretion, identically with that of 21. Compound 13 did not exhibit any agonist activity but was able to antagonize the action of gastrin (ED50 = 0.3 mg/kg). Compound 20 did not show any agonist activity but was able to inhibit gastrin-induced acid secretion, with lower potency (ED50 = 15 mg/kg). The importance of the peptide bonds in the mode of action of gastrin is discussed, and a hypothetical approach of the mechanism of action is presented.