L-缬氨酰-L-脯氨酰-L-脯氨酰-L-脯氨酰-L-缬氨酰-L-脯氨酰-L-脯氨酰-L-精氨酰-L-精氨酰-L-精氨酸 | 159088-48-9

• 物质功能分类: 生物化工 - 多肽
• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 中文名称: L-缬氨酰-L-脯氨酰-L-脯氨酰-L-脯氨酰-L-缬氨酰-L-脯氨酰-L-脯氨酰-L-精氨酰-L-精氨酰-L-精氨酸
• 英文名称: H-VPPPVPPRRR-OH
• 英文别名: Ras inhibitory peptide；(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-1-[(2S)-1-[(2S)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid
• CAS: 159088-48-9
• 化学式: C₅₃H₉₁N₁₉O₁₁
• 分子量: 1170.43
• InChiKey: KDEHBKGSNFLJSF-QMAXXTOWSA-N

物化性质

• 密度：
  1.52±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：30mg/mL； DMSO：30mg/mL；乙醇：可混溶； PBS（pH 7.2）：10 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  -5.4
• 重原子数：
  83
• 可旋转键数：
  28
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  475
• 氢给体数：
  12
• 氢受体数：
  15

安全信息

• WGK Germany：
  3

反应信息

• 作为产物：
  描述：

  BOC-L-脯氨酸 、 N-Boc-L-缬氨酸 、 N-叔丁氧羰基-N'-甲苯磺酰基-L-精氨酸 生成 L-缬氨酰-L-脯氨酰-L-脯氨酰-L-脯氨酰-L-缬氨酰-L-脯氨酰-L-脯氨酰-L-精氨酰-L-精氨酰-L-精氨酸
  参考文献：
  名称：

  High affinity Grb2-SH3 domain ligand incorporating Cβ-substituted prolines in a Sos-derived decapeptide

  摘要：

  Peptide ligands that disrupt MAPK pathways are of great interest for a better understanding of these signalling cascades and represent therefore an attractive target to control cell degenerative processes. In that context, selective disruption of the upstream Grb2/Sos complex in the Ras/MAPK cascade has focused extensive work. The Sos PPII decapeptide, which interacts with the Grb2-SH3 domains, has been modified in various positions and the best inhibitors designed so far are either dimeric ligands or peptoid analogues of the VPPPVPPRRR sequence. We report the synthesis of new Grb2 ligands in which the key Va15 residue has been replaced by a cis C-beta-substituted proline. Both fluorescence and ITC assays have been employed to measure the affinity of these substituted peptides for a recombinant Grb2 protein. Whereas proline in position 5 completely abolished the binding potency, a cis C-beta-methyl-L-proline restored the affinity. Other cis C-beta-proline substituents led to a complete loss of binding potency. Combining the best modifications: a cis C-beta-methylproline 5, N-acetylation, C-carboxamide and dimerization yielded a 560-fold affinity enhancement compared to the wild-type VPPPVPPRRR sequence. This study shows that C-beta-substituted prolines may constitute a new alternative for PPII ligands, combining entropy and enthalpy beneficial effects. C 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.002

文献信息

• High affinity Grb2-SH3 domain ligand incorporating Cβ-substituted prolines in a Sos-derived decapeptide
  作者：Yves Jacquot、Isabelle Broutin、Emeric Miclet、Magali Nicaise、Olivier Lequin、Nicole Goasdoué、Charlotte Joss、Philippe Karoyan、Michel Desmadril、Arnaud Ducruix

  DOI：10.1016/j.bmc.2006.11.002

  日期：2007.2.1

  Peptide ligands that disrupt MAPK pathways are of great interest for a better understanding of these signalling cascades and represent therefore an attractive target to control cell degenerative processes. In that context, selective disruption of the upstream Grb2/Sos complex in the Ras/MAPK cascade has focused extensive work. The Sos PPII decapeptide, which interacts with the Grb2-SH3 domains, has been modified in various positions and the best inhibitors designed so far are either dimeric ligands or peptoid analogues of the VPPPVPPRRR sequence. We report the synthesis of new Grb2 ligands in which the key Va15 residue has been replaced by a cis C-beta-substituted proline. Both fluorescence and ITC assays have been employed to measure the affinity of these substituted peptides for a recombinant Grb2 protein. Whereas proline in position 5 completely abolished the binding potency, a cis C-beta-methyl-L-proline restored the affinity. Other cis C-beta-proline substituents led to a complete loss of binding potency. Combining the best modifications: a cis C-beta-methylproline 5, N-acetylation, C-carboxamide and dimerization yielded a 560-fold affinity enhancement compared to the wild-type VPPPVPPRRR sequence. This study shows that C-beta-substituted prolines may constitute a new alternative for PPII ligands, combining entropy and enthalpy beneficial effects. C 2006 Elsevier Ltd. All rights reserved.