cyclo-<5-amino-(pentyloxycarbonyl)-tyrosyl-valyl-asparagyl-valyl-prolyl> | 225116-94-9

• 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: cyclo-<5-amino-(pentyloxycarbonyl)-tyrosyl-valyl-asparagyl-valyl-prolyl>
• 英文别名: 2-[(3S,6S,9S,12S,23S)-12-[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22-hexaoxo-3,9-di(propan-2-yl)-15-oxa-1,4,7,10,13,21-hexazabicyclo[21.3.0]hexacosan-6-yl]acetamide
• CAS: 225116-94-9
• 化学式: C₃₄H₅₁N₇O₉
• 分子量: 701.82
• InChiKey: XNVYICUEHXTZIZ-OQWKOXFXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  50
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  238
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  cyclo-<5-amino-(pentyloxycarbonyl)-tyrosyl-valyl-asparagyl-valyl-prolyl> 在 palladium on activated charcoal 四氮唑 、 叔丁基过氧化氢 、 氢气 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 cyclo-<5-amino-(pentyloxycarbonyl)-O-phosphotyrosyl-valyl-asparagyl-valyl-prolyl>
  参考文献：
  名称：

  Structural and Conformational Requirements for High-Affinity Binding to the SH2 Domain of Grb2

  摘要：

  Following earlier work on cystine-bridged peptides, cyclic phosphopeptides containing nonreducible mimics of cystine were synthesized that show high affinity and specificity toward the Src homology (SH2) domain of the growth factor receptor-binding protein (Grb2). Replacement of the cystine in the cyclic heptapeptide cyclo(CY*VNVPC) by D-alpha-acetylthialysine or D-alpha-lysine gave cyclo(Y*VNVP(D-alpha-acetyl-thiaK)) (22) and cyclo(Y*VNVP(D-alpha-acetyl-K)) (30), which showed improved binding 10-fold relative to that of the control peptide KPFY*VNVEF (1). NMR spectroscopy and molecular modeling experiments indicate that a beta-turn conformation centered around Y*VNV is essential for high-affinity binding. X-ray structure analyses show that the linear peptide 1 and the cyclic compound 21 adopt a similar binding mode with a beta-turn conformation. Our data confirm the unique structural requirements of the ligand binding site of the SH2 domain of Grb2. Moreover, the potency of our cyclic lactams can be explained by the stabilization of the beta-turn conformation by three intramolecular hydrogen bonds (one mediated by an H2O molecule). These stable and easily accessible cyclic peptides can serve as templates for the evaluation of phosphotyrosine surrogates and further chemical elaboration.

  DOI：

  10.1021/jm9811007
• 作为产物：
  描述：

  N-<(9-fluorenylmethyl)carbonyl>-asparagyl-valine 在 palladium on activated charcoal 二苯基膦叠氮化物 、 氢气 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 cyclo-<5-amino-(pentyloxycarbonyl)-tyrosyl-valyl-asparagyl-valyl-prolyl>
  参考文献：
  名称：

  Structural and Conformational Requirements for High-Affinity Binding to the SH2 Domain of Grb2

  摘要：

  Following earlier work on cystine-bridged peptides, cyclic phosphopeptides containing nonreducible mimics of cystine were synthesized that show high affinity and specificity toward the Src homology (SH2) domain of the growth factor receptor-binding protein (Grb2). Replacement of the cystine in the cyclic heptapeptide cyclo(CY*VNVPC) by D-alpha-acetylthialysine or D-alpha-lysine gave cyclo(Y*VNVP(D-alpha-acetyl-thiaK)) (22) and cyclo(Y*VNVP(D-alpha-acetyl-K)) (30), which showed improved binding 10-fold relative to that of the control peptide KPFY*VNVEF (1). NMR spectroscopy and molecular modeling experiments indicate that a beta-turn conformation centered around Y*VNV is essential for high-affinity binding. X-ray structure analyses show that the linear peptide 1 and the cyclic compound 21 adopt a similar binding mode with a beta-turn conformation. Our data confirm the unique structural requirements of the ligand binding site of the SH2 domain of Grb2. Moreover, the potency of our cyclic lactams can be explained by the stabilization of the beta-turn conformation by three intramolecular hydrogen bonds (one mediated by an H2O molecule). These stable and easily accessible cyclic peptides can serve as templates for the evaluation of phosphotyrosine surrogates and further chemical elaboration.

  DOI：

  10.1021/jm9811007

文献信息

• Structural and Conformational Requirements for High-Affinity Binding to the SH2 Domain of Grb2
  作者：Peter Ettmayer、Dennis France、John Gounarides、Mark Jarosinski、Mary-Sue Martin、Jean-Michel Rondeau、Michael Sabio、Sid Topiol、Beat Weidmann、Mauro Zurini、Kenneth W. Bair

  DOI：10.1021/jm9811007

  日期：1999.3.1

  Following earlier work on cystine-bridged peptides, cyclic phosphopeptides containing nonreducible mimics of cystine were synthesized that show high affinity and specificity toward the Src homology (SH2) domain of the growth factor receptor-binding protein (Grb2). Replacement of the cystine in the cyclic heptapeptide cyclo(CY*VNVPC) by D-alpha-acetylthialysine or D-alpha-lysine gave cyclo(Y*VNVP(D-alpha-acetyl-thiaK)) (22) and cyclo(Y*VNVP(D-alpha-acetyl-K)) (30), which showed improved binding 10-fold relative to that of the control peptide KPFY*VNVEF (1). NMR spectroscopy and molecular modeling experiments indicate that a beta-turn conformation centered around Y*VNV is essential for high-affinity binding. X-ray structure analyses show that the linear peptide 1 and the cyclic compound 21 adopt a similar binding mode with a beta-turn conformation. Our data confirm the unique structural requirements of the ligand binding site of the SH2 domain of Grb2. Moreover, the potency of our cyclic lactams can be explained by the stabilization of the beta-turn conformation by three intramolecular hydrogen bonds (one mediated by an H2O molecule). These stable and easily accessible cyclic peptides can serve as templates for the evaluation of phosphotyrosine surrogates and further chemical elaboration.