Cbz-Ala-Ala-Leu^P-(O)Phe-Ala-Ala-OMe | 128948-76-5

• 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: Cbz-Ala-Ala-Leu^P-(O)Phe-Ala-Ala-OMe
• 英文别名: [(2S)-1-[[(2S)-1-[[(2S)-1-methoxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]oxy-[(1R)-3-methyl-1-[[(2S)-2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoyl]amino]butyl]phosphinic acid
• CAS: 128948-76-5
• 化学式: C₃₅H₅₀N₅O₁₁P
• 分子量: 747.783
• InChiKey: WDXHYSRHRZPPRB-CDTWFROCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  52
• 可旋转键数：
  21
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  228
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (R)-benzyl N-[1-(dimethoxyphosphoryl)-3-methylbutyl]carbamate 在 palladium on activated charcoal N-甲基吗啉 、 甲醇 、 sodium hydroxide 、 氯化亚砜 、 三甲基溴硅烷 、 氢气 、 三乙胺 、 异丁烯 、 氯甲酸异丁酯 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 67.5h， 生成 Cbz-Ala-Ala-Leu^P-(O)Phe-Ala-Ala-OMe
  参考文献：
  名称：

  Potent inhibition of pepsin and penicillopepsin by phosphorus-containing peptide analogs

  摘要：

  Phosphinic and phosphonic acid peptide derivatives have been evaluated as inhibitors of the aspartic proteases pepsin and penicillopepsin. The most potent of those studied is isovaleryl-Val-Val-Leu(P)-(O)Phe-Ala-Ala-OMe (4) (Leu(P) represents the phosphonic acid analogue of leucine; (O)Phe represents L-beta-phenyllactic acid, the alcohol analogue of phenylalanine), for which the K(i) values for pepsin and penicillopepsin are 0.26 and 0.19 nM, respectively. While this compound binds to penicillopepsin with an association rate constant, k(on), of (6.5 +/- 1.5) X 10(5) M(-1) s(-1), it does not show slow- or two-step binding with pepsin. The binding of Cbz-Ala-Ala-Leu(P)-(O)Phe-OMe (1) to penicillopepsin is strongly dependent on pH: in comparison to pH 4.5, the affinity at pH 3.5 is increased 10-fold and at pH 5.5 it is decreased 40-fold. The two diastereomers of a nonionic phosphinamide analogue (10A, 10B) of a statine-containing inhibitor were prepared; however, both are significantly weaker inhibitors of pepsin than the phosphinic acid itself (7).

  DOI：

  10.1021/jo00313a012

文献信息

• Potent inhibition of pepsin and penicillopepsin by phosphorus-containing peptide analogs
  作者：Paul A. Bartlett、John E. Hanson、Peter P. Giannousis

  DOI：10.1021/jo00313a012

  日期：1990.12

  Phosphinic and phosphonic acid peptide derivatives have been evaluated as inhibitors of the aspartic proteases pepsin and penicillopepsin. The most potent of those studied is isovaleryl-Val-Val-Leu(P)-(O)Phe-Ala-Ala-OMe (4) (Leu(P) represents the phosphonic acid analogue of leucine; (O)Phe represents L-beta-phenyllactic acid, the alcohol analogue of phenylalanine), for which the K(i) values for pepsin and penicillopepsin are 0.26 and 0.19 nM, respectively. While this compound binds to penicillopepsin with an association rate constant, k(on), of (6.5 +/- 1.5) X 10(5) M(-1) s(-1), it does not show slow- or two-step binding with pepsin. The binding of Cbz-Ala-Ala-Leu(P)-(O)Phe-OMe (1) to penicillopepsin is strongly dependent on pH: in comparison to pH 4.5, the affinity at pH 3.5 is increased 10-fold and at pH 5.5 it is decreased 40-fold. The two diastereomers of a nonionic phosphinamide analogue (10A, 10B) of a statine-containing inhibitor were prepared; however, both are significantly weaker inhibitors of pepsin than the phosphinic acid itself (7).