N-Cbz-Val-Gly-Leu(OH) | 820239-49-4

• 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: N-Cbz-Val-Gly-Leu(OH)
• 英文别名: N-[(Benzyloxy)carbonyl]-L-valylglycyl-L-leucine；(2S)-4-methyl-2-[[2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]acetyl]amino]pentanoic acid
• CAS: 820239-49-4
• 化学式: C₂₁H₃₁N₃O₆
• 分子量: 421.494
• InChiKey: VABAJCSTWNDWNA-WMZOPIPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-Cbz-Val-Gly-Leu(OH) 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 生成 Val-Gly-Leu
  参考文献：
  名称：

  Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent

  摘要：

  Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg-1 dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of compound 30 for targeting COX-2, iNOS, and VGSC was investigated by using substance P, l-arginine, and veratrine, respectively, as biomarkers. The interactions of 30 with COX-2 were supported by isothermal calorimetry experiments showing a Ka of 6.10 +/- 1.10 X 104 M-1 and Delta G of -100.3 kJ mol-1 in comparison to a Ka 0.41 X 103 +/- 0.09 M-1 and Delta G of -19.2 +/- 0.06 kJ mol(-1) for COX-1. Moreover, compound 30 did not show toxicity up to a 2000 mg kg(-1) dose. Hence, we suggest peptide 30 as a highly potent and promising candidate for further development into an anti-inflammatory drug.

  DOI：

  10.1021/acs.jmedchem.6b00134
• 作为产物：
  描述：

  N-(N-benzyloxycarbonyl-L-valyl)-glycine 在 氯甲酸乙酯 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 13.25h， 生成 N-Cbz-Val-Gly-Leu(OH)
  参考文献：
  名称：

  Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent

  摘要：

  Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg-1 dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of compound 30 for targeting COX-2, iNOS, and VGSC was investigated by using substance P, l-arginine, and veratrine, respectively, as biomarkers. The interactions of 30 with COX-2 were supported by isothermal calorimetry experiments showing a Ka of 6.10 +/- 1.10 X 104 M-1 and Delta G of -100.3 kJ mol-1 in comparison to a Ka 0.41 X 103 +/- 0.09 M-1 and Delta G of -19.2 +/- 0.06 kJ mol(-1) for COX-1. Moreover, compound 30 did not show toxicity up to a 2000 mg kg(-1) dose. Hence, we suggest peptide 30 as a highly potent and promising candidate for further development into an anti-inflammatory drug.

  DOI：

  10.1021/acs.jmedchem.6b00134

文献信息

• Highly Diastereoselective Peptide Chain Extensions of Unprotected Amino Acids with<i>N</i>-(Z-α-Aminoacyl)benzotriazoles
  作者：Alan R. Katritzky、Kazuyuki Suzuki、Sandeep K. Singh

  DOI：10.1055/s-2004-831255

  日期：——

  Coupling an unprotected amino acid or dipeptide in partially aqueous solution with a readily available N-(Z-α-amino­acyl)benzotriazole or N-(Z-α-aminopetidoyl)benzotriazole affords N-terminal-protected di-, tri-, and tetrapeptides in yields of 85-98% (average 95% for 2a-i, 93% for 4a-f and 4a′, 86% for 5a-b) with minimal epimerization.

  在部分含水溶液中，将未保护的氨基酸或二肽与易得的N-(Z-α-氨基酰基)苯并三唑或N-(Z-α-氨基肽酰基)苯并三唑结合，可以以85-98%的产率（平均产率分别为2a-i的95%，4a-f和4a′的93%，5a-b的86%）获得N端保护的二肽、三肽和四肽，且消旋化程度最小。
• Temperature, pH and H-bond synergism for peptide bond formation: synthesis of sequence specific tetra- and penta-peptides without using coupling reagent
  作者：Palwinder Singh、Amrinder Singh、Sukhmeet Kaur、Venus Singh Mithu、Manpreet S. Bhatti

  DOI：10.1039/c4ra06187j

  日期：——

  A reaction temperature of 120 °C, pH of 5.0 and reaction time of 6 h were chosen as the best conditions for the condensation of two nonactivated amino acids to form a peptide bond. Role of H-bond in these reactions was anticipated. The method was validated by procuring sequence specific tetrapeptides and pentapeptides without any disturbance to their chirality.

  选择反应温度120℃、pH 5.0和反应时间6h作为两个未活化氨基酸缩合形成肽键的最佳条件。氢键在这些反应中的作用是预期的。该方法通过获得序列特异性四肽和五肽而对其手性没有任何干扰进行了验证。
• Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent
  作者：Palwinder Singh、Sukhmeet Kaur、Jagroop Kaur、Gurjit Singh、Rajbir Bhatti

  DOI：10.1021/acs.jmedchem.6b00134

  日期：2016.4.28

  Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg-1 dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of compound 30 for targeting COX-2, iNOS, and VGSC was investigated by using substance P, l-arginine, and veratrine, respectively, as biomarkers. The interactions of 30 with COX-2 were supported by isothermal calorimetry experiments showing a Ka of 6.10 +/- 1.10 X 104 M-1 and Delta G of -100.3 kJ mol-1 in comparison to a Ka 0.41 X 103 +/- 0.09 M-1 and Delta G of -19.2 +/- 0.06 kJ mol(-1) for COX-1. Moreover, compound 30 did not show toxicity up to a 2000 mg kg(-1) dose. Hence, we suggest peptide 30 as a highly potent and promising candidate for further development into an anti-inflammatory drug.