N-Fmoc-S-trityl-L-cysteinyl-(2S,5R)-5-tert-butylproline | 268219-98-3

• 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: N-Fmoc-S-trityl-L-cysteinyl-(2S,5R)-5-tert-butylproline
• 英文别名: (2S,5R)-5-tert-butyl-1-[(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-tritylsulfanylpropanoyl]pyrrolidine-2-carboxylic acid
• CAS: 268219-98-3
• 化学式: C₄₆H₄₆N₂O₅S
• 分子量: 738.948
• InChiKey: OFNDVBRGZMXQNQ-YZBUDRBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.9
• 重原子数：
  54
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(三苯甲硫基)丙酸 、 Fmoc-L-异亮氨酸 、 Fmoc-O-叔丁基-L-酪氨酸 、 N-Fmoc-S-trityl-L-cysteinyl-(2S,5R)-5-tert-butylproline 、 alkaline earth salt of/the/ methylsulfuric acid 生成 [Mpa(H)¹,Cys(H)⁶,5-t-BuPro⁷]oxytocin
  参考文献：
  名称：

  A Study of the Relationship between Biological Activity and Prolyl Amide Isomer Geometry in Oxytocin Using 5-tert-Butylproline To Augment the Cys⁶-Pro⁷ Amide Cis-Isomer Population

  摘要：

  Three [5-t-BuPro(7)]oxytocin analogues were synthesized by substituting (2S,5R)-5-tert-butyl-proline for proline in oxytocin, [Mpa(1)]oxytocin, and [dPen(1)]oxytocin. Relative to oxytocin, [5-t-BuPro(7)]oxytocin and [Mpa(1),5-t-BuPro(7)]oxytocin exhibited strongly reduced binding affinity to the receptor; however, both peptides maintained the pharmacophore characteristics responsible for signal transfer evoking the same maximal response as oxytocin in the single-dose procedure and exhibiting partial agonistic activity in the cumulative dose-response procedure. Although [dPen(1)]oxytocin exhibited inhibitory as well as partial agonistic activity, [dPen(1),5-t-BuPro(7)]oxytocin exhibited only inhibitory potency with a similar in vitro pA(2) value of 7.50 in the absence of magnesium. In the presence of magnesium, [dPen(1),5-t-BuPro7]oxytocin exhibited stronger inhibitory potency than [dPen(1)]oxytocin and no partial agonism. Assignment of the proton signals for the 5-tert-butylprolyl amide cis- and trans-isomers by two-dimensional NMR experiments in water indicated that the Cys(6)-Pro(7) peptide bond cis-isomer population was augmented relative to the prolyl peptides and measured respectively at 35%, 33%, and 20% in the 5-tert-butylproline(7) analogues of oxytocin, [Mpa(1)]oxytocin and [dPen(1)]oxytocin. Although caution must be taken when relating the increase in cis-isomer population with an influence on biological activity in [5-t-BuPro7(])oxytocin analogues, the synthesis and evaluation of analogues 1-3 have provided additional evidence that can be used to support the hypothesis that the prolyl amide cis-isomer may favor antagonism and the trans-isomer is necessary for agonist activity.

  DOI：

  10.1021/jm990090m
• 作为产物：
  描述：

  N-Fmoc-S-trityl-L-cysteinyl-(2S,5R)-5-tert-butylproline allyl ester 在 (PdPh₃)2Cl₂ 、 三正丁基氢锡 作用下， 以 二氯甲烷 为溶剂， 以96%的产率得到N-Fmoc-S-trityl-L-cysteinyl-(2S,5R)-5-tert-butylproline
  参考文献：
  名称：

  A Study of the Relationship between Biological Activity and Prolyl Amide Isomer Geometry in Oxytocin Using 5-tert-Butylproline To Augment the Cys⁶-Pro⁷ Amide Cis-Isomer Population

  摘要：

  Three [5-t-BuPro(7)]oxytocin analogues were synthesized by substituting (2S,5R)-5-tert-butyl-proline for proline in oxytocin, [Mpa(1)]oxytocin, and [dPen(1)]oxytocin. Relative to oxytocin, [5-t-BuPro(7)]oxytocin and [Mpa(1),5-t-BuPro(7)]oxytocin exhibited strongly reduced binding affinity to the receptor; however, both peptides maintained the pharmacophore characteristics responsible for signal transfer evoking the same maximal response as oxytocin in the single-dose procedure and exhibiting partial agonistic activity in the cumulative dose-response procedure. Although [dPen(1)]oxytocin exhibited inhibitory as well as partial agonistic activity, [dPen(1),5-t-BuPro(7)]oxytocin exhibited only inhibitory potency with a similar in vitro pA(2) value of 7.50 in the absence of magnesium. In the presence of magnesium, [dPen(1),5-t-BuPro7]oxytocin exhibited stronger inhibitory potency than [dPen(1)]oxytocin and no partial agonism. Assignment of the proton signals for the 5-tert-butylprolyl amide cis- and trans-isomers by two-dimensional NMR experiments in water indicated that the Cys(6)-Pro(7) peptide bond cis-isomer population was augmented relative to the prolyl peptides and measured respectively at 35%, 33%, and 20% in the 5-tert-butylproline(7) analogues of oxytocin, [Mpa(1)]oxytocin and [dPen(1)]oxytocin. Although caution must be taken when relating the increase in cis-isomer population with an influence on biological activity in [5-t-BuPro7(])oxytocin analogues, the synthesis and evaluation of analogues 1-3 have provided additional evidence that can be used to support the hypothesis that the prolyl amide cis-isomer may favor antagonism and the trans-isomer is necessary for agonist activity.

  DOI：

  10.1021/jm990090m

文献信息

• A Study of the Relationship between Biological Activity and Prolyl Amide Isomer Geometry in Oxytocin Using 5-<i>tert</i>-Butylproline To Augment the Cys⁶-Pro⁷ Amide <i>Cis</i>-Isomer Population
  作者：Laurent Bélec、Jirina Slaninova、William D. Lubell

  DOI：10.1021/jm990090m

  日期：2000.4.1

  Three [5-t-BuPro(7)]oxytocin analogues were synthesized by substituting (2S,5R)-5-tert-butyl-proline for proline in oxytocin, [Mpa(1)]oxytocin, and [dPen(1)]oxytocin. Relative to oxytocin, [5-t-BuPro(7)]oxytocin and [Mpa(1),5-t-BuPro(7)]oxytocin exhibited strongly reduced binding affinity to the receptor; however, both peptides maintained the pharmacophore characteristics responsible for signal transfer evoking the same maximal response as oxytocin in the single-dose procedure and exhibiting partial agonistic activity in the cumulative dose-response procedure. Although [dPen(1)]oxytocin exhibited inhibitory as well as partial agonistic activity, [dPen(1),5-t-BuPro(7)]oxytocin exhibited only inhibitory potency with a similar in vitro pA(2) value of 7.50 in the absence of magnesium. In the presence of magnesium, [dPen(1),5-t-BuPro7]oxytocin exhibited stronger inhibitory potency than [dPen(1)]oxytocin and no partial agonism. Assignment of the proton signals for the 5-tert-butylprolyl amide cis- and trans-isomers by two-dimensional NMR experiments in water indicated that the Cys(6)-Pro(7) peptide bond cis-isomer population was augmented relative to the prolyl peptides and measured respectively at 35%, 33%, and 20% in the 5-tert-butylproline(7) analogues of oxytocin, [Mpa(1)]oxytocin and [dPen(1)]oxytocin. Although caution must be taken when relating the increase in cis-isomer population with an influence on biological activity in [5-t-BuPro7(])oxytocin analogues, the synthesis and evaluation of analogues 1-3 have provided additional evidence that can be used to support the hypothesis that the prolyl amide cis-isomer may favor antagonism and the trans-isomer is necessary for agonist activity.