Ac-LPFFD-NH₂

• 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: Ac-LPFFD-NH₂
• 英文别名: Ac-Leu-Pro-Phe-Phe-Asp-NH₂；(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-Acetamido-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-amino-4-oxobutanoic acid
• 化学式: C₃₅H₄₆N₆O₈
• 分子量: 678.786
• InChiKey: DFIDZYQHBGZLHZ-ZIUUJSQJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  49
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  217
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Ac-LPFFD-NH₂ 在 重水 作用下， 生成
  参考文献：
  名称：

  Synthesis and activity of fibrillogenesis peptide inhibitors related to the 17–21 β-amyloid sequence

  摘要：

  Peptide derivatives 1-5, incorporating synthetic non-proteinogenic amino acids, related to the beta-amyloid 17-21 fragment of the amyloidogenic A beta(1-40), and the N-protected decapeptide 6, corresponding to a dimeric sequence of the same fragment, have been synthesized. These compounds were designed by using Soto's pentapeptide Ac-LPFFD-NH2 (iA beta 5p) as lead compound. Their activity as inhibitors of fibrillogenesis and stability against enzymatic degradation have been determined. Compounds 1, 5 and 6 are potent inhibitors in comparison to the lead compound. Exposure to chymotrypsin of peptide derivatives 1-5, all containing unnatural amino acids, shows increased stability as compared with iA beta 5p and 6. Conformational properties of the new compounds have been determined by CD and FF-IR spectroscopies. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.03.036
• 作为产物：
  描述：

  Fmoc-L-亮氨酸 、 Fmoc-L-脯氨酸 、 Fmoc-L-苯丙氨酸 、 Fmoc-L-天冬氨酸 beta-叔丁酯 、 乙酸酐 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Ac-LPFFD-NH₂
  参考文献：
  名称：

  Protective effects of β-sheet breaker α/β-hybrid peptide against amyloid β-induced neuronal apoptosis in vitro

  摘要：

  Alzheimer's disease is most common neurodegenerative disorder and is characterized by increased production of soluble amyloid‐β oligomers, the main toxic species predominantly formed from aggregation of monomeric amyloid‐β (Aβ). Increased production of Aβ invokes a cascade of oxidative damages to neurons and eventually leads to neuronal death. This study was aimed to investigate the neuroprotective effects of a β‐sheet breaker α/β‐hybrid peptide (BSBHp) and the underlying mechanisms against Aβ40‐induced neurotoxicity in human neuroblastoma SH‐SY5Y cells. Cells were pretreated with the peptide Aβ40 to induce neurotoxicity. Assays for cell viability, cell membrane damage, cellular apoptosis, generation of reactive oxygen species (ROS), intracellular free Ca2+, and key apoptotic protein levels were performed in vitro. Our results showed that pretreatment with BSBHp significantly attenuates Aβ40‐induced toxicity by retaining cell viability, suppressing generation of ROS, Ca2+ levels, and effectively protects neuronal apoptosis by suppressing pro‐apoptotic protein Bax and up‐regulating antiapoptotic protein Bcl‐2. These results suggest that α/β‐hybrid peptide has neuroprotective effects against Aβ40‐induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.

  DOI：

  10.1111/cbdd.12912

文献信息

• Synthesis and activity of fibrillogenesis peptide inhibitors related to the 17–21 β-amyloid sequence
  作者：Cesare Giordano、Annalisa Masi、Aldo Pizzini、Anna Sansone、Valerio Consalvi、Roberta Chiaraluce、Gino Lucente

  DOI：10.1016/j.ejmech.2008.03.036

  日期：2009.1

  Peptide derivatives 1-5, incorporating synthetic non-proteinogenic amino acids, related to the beta-amyloid 17-21 fragment of the amyloidogenic A beta(1-40), and the N-protected decapeptide 6, corresponding to a dimeric sequence of the same fragment, have been synthesized. These compounds were designed by using Soto's pentapeptide Ac-LPFFD-NH2 (iA beta 5p) as lead compound. Their activity as inhibitors of fibrillogenesis and stability against enzymatic degradation have been determined. Compounds 1, 5 and 6 are potent inhibitors in comparison to the lead compound. Exposure to chymotrypsin of peptide derivatives 1-5, all containing unnatural amino acids, shows increased stability as compared with iA beta 5p and 6. Conformational properties of the new compounds have been determined by CD and FF-IR spectroscopies. (C) 2008 Elsevier Masson SAS. All rights reserved.
• Protective effects of β-sheet breaker α/β-hybrid peptide against amyloid β-induced neuronal apoptosis in vitro
  作者：Sourav Kumar、Ashim Paul、Sourav Kalita、Anup Kumar Ghosh、Bhubaneswar Mandal、Amal Chandra Mondal

  DOI：10.1111/cbdd.12912

  日期：2017.6

  Alzheimer's disease is most common neurodegenerative disorder and is characterized by increased production of soluble amyloid‐β oligomers, the main toxic species predominantly formed from aggregation of monomeric amyloid‐β (Aβ). Increased production of Aβ invokes a cascade of oxidative damages to neurons and eventually leads to neuronal death. This study was aimed to investigate the neuroprotective effects of a β‐sheet breaker α/β‐hybrid peptide (BSBHp) and the underlying mechanisms against Aβ40‐induced neurotoxicity in human neuroblastoma SH‐SY5Y cells. Cells were pretreated with the peptide Aβ40 to induce neurotoxicity. Assays for cell viability, cell membrane damage, cellular apoptosis, generation of reactive oxygen species (ROS), intracellular free Ca2+, and key apoptotic protein levels were performed in vitro. Our results showed that pretreatment with BSBHp significantly attenuates Aβ40‐induced toxicity by retaining cell viability, suppressing generation of ROS, Ca2+ levels, and effectively protects neuronal apoptosis by suppressing pro‐apoptotic protein Bax and up‐regulating antiapoptotic protein Bcl‐2. These results suggest that α/β‐hybrid peptide has neuroprotective effects against Aβ40‐induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.