H-L-Ala-D-Pro-O^tBu | 97372-40-2

• 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: H-L-Ala-D-Pro-O^tBu
• 英文别名: L-Ala-D-Pro-O^tBu；L-Ala-D-Pro-O^tBu；tert-butyl (2R)-1-[(2S)-2-aminopropanoyl]pyrrolidine-2-carboxylate
• CAS: 97372-40-2
• 化学式: C₁₂H₂₂N₂O₃
• 分子量: 242.318
• InChiKey: GEMSXPOJLIUVKT-DTWKUNHWSA-N

物化性质

• 沸点：
  358.2±37.0 °C(Predicted)
• 密度：
  1.107±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.67
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  72.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  H-L-Ala-D-Pro-O^tBu 在 盐酸 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 cyclo[Ala-D-Pro-Nle(Unk)-D-Nle(Unk)]
  参考文献：
  名称：

  RETRACTED: Design and synthesis of CHAP31, trapoxin B and HC-toxin based bicyclic tetrapeptides disulfide as potent histone deacetylase inhibitors

  摘要：

  The naturally occurring cyclic depsipeptide, FK228 inhibits histone deacetylase (HDAC) enzymes after reductive cleavage of intra-molecular disulfide bond. One of the sulfhydryl groups produced in the reduction interacts with zinc atom that involved in the catalytic mechanism of type 1 and 2 HDACs such as HDAC1, HDAC4, and HDAC6. In the present study, we describe the development of CHAP31, trapoxin B and HC-toxin based cyclic tetrapeptides with intra-molecular disulfide bond as HDAC inhibitors. The bicyclic tetrapeptides disulfide showed potent HDAC1 and HDAC4 inhibition and p21 promoting activity.

  DOI：

  10.1016/j.bmc.2014.06.029
• 作为产物：
  描述：

  Z-L-Ala-D-Pro-OtBu 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 反应 10.0h， 以99%的产率得到H-L-Ala-D-Pro-O^tBu
  参考文献：
  名称：

  衣藻素框架中芳香环移位对组蛋白脱乙酰基酶抑制剂的分子设计。

  摘要：

  衣霉素，一种环状四肽，含有氨基异丁酸（Aib），1-苯丙氨酸（1-Phe），d-脯氨酸（d-Pro）和独特的氨基酸1-2-氨基-8-氧代-9,10-环氧癸酸酸抑制组蛋白脱乙酰酶（HDACs），HDAC是一类酶，在调节基因表达中起重要作用。含硫的氨基酸也可以有效抑制，因此在衣原霉素的情况下，与配体环状四肽构架相对应的锌配体（例如与连接到所谓的封端基团的封端基团相连的巯基）应与HDAC分子表面相互作用。衣原霉素中氨基酸残基的各种变化可提供针对HDAC旁系同源物的特异性抑制剂。为了找出特定的抑制剂，我们着重研究了衣藻素框架中1-苯丙氨酸的苯环，以转移至环状四肽的各个部分。我们制备了几种芳香族氨基酸并将其引入到环状四肽中。通过评估这些大环肽对HDAC的抑制活性，我们可以通过将芳香环转移到Aib位点来找到有效的抑制剂。

  DOI：

  10.1016/j.bmc.2007.08.041

文献信息

• Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework
  作者：Gururaj M. Shivashimpi、Satoshi Amagai、Tamaki Kato、Norikazu Nishino、Satoko Maeda、Tomonori G. Nishino、Minoru Yoshida

  DOI：10.1016/j.bmc.2007.08.041

  日期：2007.12

  capping group, corresponding to cyclic tetrapeptide framework in case of chlamydocin is supposed to interact with the surface of HDAC molecule. Various changes in amino acid residues in chlamydocin may afford specific inhibitors toward HDAC paralogs. To find out specific inhibitors, we focused on benzene ring of l-Phe in chlamydocin framework to shift to various parts of cyclic tetrapeptide. We prepared

  衣霉素，一种环状四肽，含有氨基异丁酸（Aib），1-苯丙氨酸（1-Phe），d-脯氨酸（d-Pro）和独特的氨基酸1-2-氨基-8-氧代-9,10-环氧癸酸酸抑制组蛋白脱乙酰酶（HDACs），HDAC是一类酶，在调节基因表达中起重要作用。含硫的氨基酸也可以有效抑制，因此在衣原霉素的情况下，与配体环状四肽构架相对应的锌配体（例如与连接到所谓的封端基团的封端基团相连的巯基）应与HDAC分子表面相互作用。衣原霉素中氨基酸残基的各种变化可提供针对HDAC旁系同源物的特异性抑制剂。为了找出特定的抑制剂，我们着重研究了衣藻素框架中1-苯丙氨酸的苯环，以转移至环状四肽的各个部分。我们制备了几种芳香族氨基酸并将其引入到环状四肽中。通过评估这些大环肽对HDAC的抑制活性，我们可以通过将芳香环转移到Aib位点来找到有效的抑制剂。
• Interaction of aliphatic cap group in inhibition of histone deacetylases by cyclic tetrapeptides
  作者：Norikazu Nishino、Gururaj M. Shivashimpi、Preeti B. Soni、Mohammed P.I. Bhuiyan、Tamaki Kato、Satoko Maeda、Tomonori G. Nishino、Minoru Yoshida

  DOI：10.1016/j.bmc.2007.09.021

  日期：2008.1

  Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that effect gene regulation. To know the interaction of aliphatic cap groups with HDACs, cyclic tetrapeptide and bicyclic peptide disulfide hybrids were synthesized without aromatic ring in their macrocyclic framework. Benzene ring Of L-Phe in chlamydocin was replaced with several aliphatic amino acids and also a fused bicyclic tetrapeptide was synthesized by ring closing metathesis using Grubb's first generation catalyst. The inhibitory activities of the cyclic peptides against historic deacetylase enzymes were evaluated, which demonstrated most of them are interesting candidates as anticancer agents. (c) 2007 Elsevier Ltd. All rights reserved.
• RETRACTED: Design and synthesis of CHAP31, trapoxin B and HC-toxin based bicyclic tetrapeptides disulfide as potent histone deacetylase inhibitors
  作者：Md. Ashraful Hoque、Md. Nurul Islam、Md. Shahidul Islam、Tamaki Kato、Norikazu Nishino、Akihiro Ito、Minoru Yoshida

  DOI：10.1016/j.bmc.2014.06.029

  日期：2014.8

  The naturally occurring cyclic depsipeptide, FK228 inhibits histone deacetylase (HDAC) enzymes after reductive cleavage of intra-molecular disulfide bond. One of the sulfhydryl groups produced in the reduction interacts with zinc atom that involved in the catalytic mechanism of type 1 and 2 HDACs such as HDAC1, HDAC4, and HDAC6. In the present study, we describe the development of CHAP31, trapoxin B and HC-toxin based cyclic tetrapeptides with intra-molecular disulfide bond as HDAC inhibitors. The bicyclic tetrapeptides disulfide showed potent HDAC1 and HDAC4 inhibition and p21 promoting activity.