H-Val-Leu-OMe*TFA

• 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-Val-Leu-OMe*TFA
• 英文别名: methyl (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-4-methylpentanoate;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₁₂H₂₄N₂O₃
• 分子量: 358.358
• InChiKey: RXEZXKICEQCJFU-IYPAPVHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.31
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  H-Val-Leu-OMe*TFA 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-[(S)-3-Isopropyl-4-(4-nitro-benzenesulfonyl)-2-oxo-piperazin-1-yl]-4-methyl-pentanoic acid methyl ester
  参考文献：
  名称：

  Efficient synthesis of substituted oxopiperazines from amino acids

  摘要：

  The synthesis of substituted oxopiperazines, which may act as conformationally constrained peptide mimics, is reported. The synthesis is based on the cyclization of sulfonamide dipeptides with dibromoethane as the 1, 2-dielectrophile. Alternatively, these mimetics were prepared via a Mitsunobu reaction. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)01878-4
• 作为产物：
  描述：

  L-亮氨酸甲酯盐酸盐 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.5h， 生成 H-Val-Leu-OMe*TFA
  参考文献：
  名称：

  Efficient synthesis of substituted oxopiperazines from amino acids

  摘要：

  The synthesis of substituted oxopiperazines, which may act as conformationally constrained peptide mimics, is reported. The synthesis is based on the cyclization of sulfonamide dipeptides with dibromoethane as the 1, 2-dielectrophile. Alternatively, these mimetics were prepared via a Mitsunobu reaction. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)01878-4

文献信息

• The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands
  作者：Yaochun Xu、Isabelle Correia、Tap Ha-Duong、Nadjib Kihal、Jean-Louis Soulier、Julia Kaffy、Benoît Crousse、Olivier Lequin、Sandrine Ongeri

  DOI：10.3762/bjoc.13.276

  日期：——

  studies and molecular dynamics simulations. CF3-threonine containing pentapeptides are more prone to mimic β-strands than their natural Ser and Thr pentapeptide analogues. The proof of concept that these fluorinated β-strand mimics are able to disrupt protein-protein interactions involving β-sheet structures is provided. The CF3-threonine containing pentapeptides interact with the amyloid peptide Aβ1-42

  具有序列R-HN-Ala-Val-X-Val-Leu-OMe的五肽，其中中心残基X为L-丝氨酸，L-苏氨酸，（2S，3R）-L-CF3-苏氨酸和（2S，3S制备了-L-CF 3-苏氨酸。NMR构象研究和分子动力学模拟证明了（2S，3S）-和（2S，3R）- -苏氨酸类似物在引入五肽中心位置时稳定扩展结构的能力。含 -苏氨酸的五肽比其天然Ser和Thr五肽类似物更容易模拟β链。提供了这些氟化的β-链模拟物能够破坏涉及β-折叠结构的蛋白质-蛋白质相互作用的概念证明。
• Synthesis and Host−Guest Studies of Chiral <i>N</i>-Linked Peptidoresorc[4]arenes
  作者：Bruno Botta、Ilaria D'Acquarica、Giuliano Delle Monache、Deborah Subissati、Gloria Uccello-Barretta、Massimo Mastrini、Samuele Nazzi、Maurizio Speranza

  DOI：10.1021/jo7016636

  日期：2007.11.1

  (10, 11, ent-10, and ent-11) tetrafunctionalized at the feet with valyl-leucine [ll- (6); dd- (ent-6)] and leucyl-valine [ll- (9); dd- (ent-9)] methyl esters have been synthesized. These compounds, obtained by conjugation of macrocycle tetracarboxylic acid chlorides with the appropriate terminal amino groups of the above dipeptides, are N-linked peptidoresorc[4]arenes. We found that these macrocycles

  四个锥体resorc [4]芳烃八甲基醚（10，11，耳鼻喉科- 10，和ENT - 11）在与缬氨酰基-亮氨酸[脚tetrafunctionalized LL - （6）; dd-（eNT - 6）]和亮氨酰缬氨酸[ ll-（9）; dd-（eNT - 9）]甲酯已经合成。通过使大环四羧酸氯化物与上述二肽的适当末端氨基缀合而获得的这些化合物是N连接的肽间苯二酚[4]芳烃。我们发现这些大环化合物（M）通过形成相对稳定的宿主-客体复合物（[M·G]），能够抵抗色谱纯化，从而在溶液和气相中均能够将同系物二肽识别为客体（G）。但不要加热。通过NMR方法（包括NMR DOSY实验）研究了溶液中M和G之间的络合现象，以检测平移扩散。通过Foster-Fyfe方法获得的配合物[ 10 · 6 ]和[ 10 · eNT - 6的杂合常数为2030和186 M -1分别与二肽本身的自缔合常数相当。相反，通
• Classical Synthesis of and Structural Studies on a Biologically Active Heptapeptide and a Nonapeptide of Bovine Elastin
  作者：Caterina Spezzacatena、Tiziana Perri、Valeria Guantieri、Lawrence B. Sandberg、Thomas F. Mitts、Antonio M. Tamburro

  DOI：10.1002/1099-0690(20021)2002:1<95::aid-ejoc95>3.0.co;2-l

  日期：2002.1

  disorder with respect to the “monomer”, the molecular conformation being accountable for by unstructured polypeptide chains together with β-turns. The polymer is able to adopt supramolecular structures reminiscent of those found in elastin. Unlike that of the heptapeptide, polycondensation of the nonapeptide did not afford a linear polymer, but only cyclic derivatives. This could well be due to the tendency

  描述了结合结构单元 XGGXG (X = A) 的两个弹性蛋白序列的合成。特别地，合成并表征了以下肽和多肽：TFA-H2+LGAGGAG-OH、TFA-H2+LGAGGAGVL-OH（这两者均在培养的成人成纤维细胞中诱导内源弹性蛋白产生的刺激）、聚（LGAGGAG）、和聚（LGAGGAGVL）。该合成通过经典方法在溶液中完成，缩聚步骤使用二苯基磷酰基叠氮化物，偶联步骤使用混合酸酐方法。CD、NMR 和 FT-IR 测量表明，准扩展 (PP II) 结构是七肽中的一种特殊结构特征，并且在九肽中倾向于灵活的 β-转角。聚（LGAGGAG）在“单体”方面表现出更大的无序，分子构象由非结构化多肽链和 β-转角构成。该聚合物能够采用与弹性蛋白中发现的超分子结构相似的超分子结构。与七肽的缩聚不同，九肽的缩聚不提供线性聚合物，而仅提供环状衍生物。这很可能是由于单体九肽倾向于采用折叠构象。
• Synthesis and Peptide Binding Properties of Methoxypyrrole Amino Acids (MOPAS)
  作者：Christoph Bonauer、Manfred Zabel、Burkhard König

  DOI：10.1021/ol049855x

  日期：2004.4.1

  [structure: see text] Methoxypyrrole amino acids (MOPAS) have been prepared and were introduced into small peptides with hairpin structures. The intra- and intermolecular binding properties of this heterocyclic amino acid mimicking a dipeptido beta-strand was investigated by NMR titration and X-ray crystal structure analysis. The data reveal a hydrogen bonding pattern that is complementary to a peptide

  [结构：见正文]甲氧基吡咯氨基酸（MOPAS）已制备，并被引入具有发夹结构的小肽中。通过NMR滴定和X射线晶体结构分析研究了该模仿二肽β-链的杂环氨基酸的分子内和分子间结合特性。数据揭示了与肽β-折叠互补的氢键模式。
• Lead Optimization of 2-Phenylindolylglyoxylyldipeptide Murine Double Minute (MDM)2/Translocator Protein (TSPO) Dual Inhibitors for the Treatment of Gliomas
  作者：Simona Daniele、Valeria La Pietra、Elisabetta Barresi、Salvatore Di Maro、Eleonora Da Pozzo、Marco Robello、Concettina La Motta、Sandro Cosconati、Sabrina Taliani、Luciana Marinelli、Ettore Novellino、Claudia Martini、Federico Da Settimo

  DOI：10.1021/acs.jmedchem.5b01767

  日期：2016.5.26

  In glioblastoma multiforme (GBM), translocator protein (TSPO) and murine double minute (MDM)2/p53 complex represent two druggable targets. We recently reported the first dual binder 3 possessing a higher anticancer effect in GBM cells than the standards PK11195 1 or Nutlin-3 2 singularly applied. Herein, through a structure activity relationship study, we developed derivatives 4-10 with improved potencies toward both TSPO and MDM2. As a result, compound 9: (i) reactivated the p53 functionality; (ii) inhibited the viability of two human GBM cells; (iii) impaired the proliferation of glioma cancer stem cells (CSCs), more resistant to chemotherapeutics and responsible of GBM recurrence; (iv) sensitized GBM cells and CSCs to the activity of temozolomide; (v) directed its effects preferentially toward tumor cells with respect to healthy ones. Thus, 9 may represent a promising cytotoxic agent, which is worthy of being further developed for a therapeutic approach against GBM, where the downstream p53 signaling is intact and TSPO is overexpressed.