cyclo1(OMS)-Pro²-Phe³ΨGly⁴-Pro⁵-Ahx⁶>

• 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: cyclo1(OMS)-Pro²-Phe³ΨGly⁴-Pro⁵-Ahx⁶>
• 英文别名: [(3S,6S,9S,21S)-18-benzyl-6-butyl-17-hydroxy-2,5,8,14,17,20-hexaoxo-1,4,7,13,19-pentaza-17lambda5-phosphatricyclo[19.3.0.09,13]tetracosan-3-yl]methyl methanesulfonate；[(3S,6S,9S,21S)-18-benzyl-6-butyl-17-hydroxy-2,5,8,14,17,20-hexaoxo-1,4,7,13,19-pentaza-17λ5-phosphatricyclo[19.3.0.09,13]tetracosan-3-yl]methyl methanesulfonate
• 化学式: C₃₁H₄₆N₅O₁₀PS
• 分子量: 711.774
• InChiKey: OGLAWQHOTTXVRR-RKLPTUIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  48
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  217
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  cyclo1(OMS)-Pro²-Phe³ΨGly⁴-Pro⁵-Ahx⁶> 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 cyclo<ΔAla¹-Pro²-D-Phe³ΨGly⁴-Pro⁵-Ahx⁶> 、 cyclo<ΔAla¹-Pro²-Phe³ΨGly⁴-Pro⁵-Ahx⁶>
  参考文献：
  名称：

  Cyclic Peptides with a Phosphinic Bond as Potent Inhibitors of a Zinc Bacterial Collagenase

  摘要：

  A series of cyclic peptides containing a phosphinic bond were synthesized and evaluated as inhibitors of a zinc bacterial collagenase from Corynebacterium rathaii. Among this series of pseudopeptides of different sizes of cycles, only two molecules Ia (cycto[Gly-Pro-Phe Psi(PO2CH2)-Gly-Pro-Ahx]) and Va (cyclo[beta Ala-Pro-Phe Psi(PO2CH2)Gly-Pro-Ahx]) were found to be rather potent inhibitors of this protease, with K-i values of 120 and 90 nM, respectively. Besides the influence of the peptide ring size, this study suggests that both the stereochemical and the conformational properties of the pseudophenylalanine residue in these cyclic peptides may determine their potency. Interestingly, the kinetic analysis for the binding of the cyclic peptide inhibitors Ia and Va to the collagenase, as compared to a linear parent compound, reveals that the lower potency of the cyclic peptides is mostly the consequence of a lower rate constant for association to the enzyme. To our knowledge, this is the first report on cyclic phosphinic peptides and on their activities as inhibitors of a zinc protease.

  DOI：

  10.1021/jm00043a011
• 作为产物：
  描述：

  甲基磺酰氯 、 cyclo1-Pro²-Phe³ΨGly⁴-Pro⁵-Ahx⁶> 在 吡啶 作用下， 反应 24.0h， 以68%的产率得到cyclo1(OMS)-Pro²-Phe³ΨGly⁴-Pro⁵-Ahx⁶>
  参考文献：
  名称：

  Cyclic Peptides with a Phosphinic Bond as Potent Inhibitors of a Zinc Bacterial Collagenase

  摘要：

  A series of cyclic peptides containing a phosphinic bond were synthesized and evaluated as inhibitors of a zinc bacterial collagenase from Corynebacterium rathaii. Among this series of pseudopeptides of different sizes of cycles, only two molecules Ia (cycto[Gly-Pro-Phe Psi(PO2CH2)-Gly-Pro-Ahx]) and Va (cyclo[beta Ala-Pro-Phe Psi(PO2CH2)Gly-Pro-Ahx]) were found to be rather potent inhibitors of this protease, with K-i values of 120 and 90 nM, respectively. Besides the influence of the peptide ring size, this study suggests that both the stereochemical and the conformational properties of the pseudophenylalanine residue in these cyclic peptides may determine their potency. Interestingly, the kinetic analysis for the binding of the cyclic peptide inhibitors Ia and Va to the collagenase, as compared to a linear parent compound, reveals that the lower potency of the cyclic peptides is mostly the consequence of a lower rate constant for association to the enzyme. To our knowledge, this is the first report on cyclic phosphinic peptides and on their activities as inhibitors of a zinc protease.

  DOI：

  10.1021/jm00043a011