(S)-2-((tert-butoxycarbonyl)amino)-3-(7-(diethylamino)-2-oxo-2H-chromene-3-carboxamido)propanoic acid | 1433874-93-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: (S)-2-((tert-butoxycarbonyl)amino)-3-(7-(diethylamino)-2-oxo-2H-chromene-3-carboxamido)propanoic acid
• 英文别名: (2S)-3-[[7-(diethylamino)-2-oxochromene-3-carbonyl]amino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 1433874-93-1
• 化学式: C₂₂H₂₉N₃O₇
• 分子量: 447.488
• InChiKey: QMAZRHPEKIUOEC-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  134
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-2-((tert-butoxycarbonyl)amino)-3-(7-(diethylamino)-2-oxo-2H-chromene-3-carboxamido)propanoic acid 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  核糖体介导的荧光氨基酸体外掺入肽

  摘要：

  我们报告了各种荧光氨基酸（FAA）的设计，化学合成和弹性酶催化的转移RNA（tRNA）酰化。荧光基团包括pyr，香豆素，硝基苯并恶二唑和荧光素变体。我们进一步证明通过遗传密码重编程在体外通过核糖体将FAA特异掺入肽中。

  DOI：

  10.1039/d0cc07740b
• 作为产物：
  描述：

  BOC-L-天冬酰胺 在 碘苯二乙酸 、 N,N-二异丙基乙胺 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.5h， 生成 (S)-2-((tert-butoxycarbonyl)amino)-3-(7-(diethylamino)-2-oxo-2H-chromene-3-carboxamido)propanoic acid
  参考文献：
  名称：

  Fluorescently Labeled Amino Acids as Building Blocks for Bioactive Molecules

  摘要：

  A series of twelve fluorescently labeled amino acids were designed by assembling different coumarin, fluorescein, or nitrobenzofurazan fluorophores with N-protected lysine or 2-aminopropionic acid. The synthesized amino acids were evaluated with regard to their spectroscopic properties. The easy introduction of the amino acids into peptides and peptidomimetics was exemplarily shown for one coumarin-labeled amino acid.

  DOI：

  10.1055/s-0035-1560361

文献信息

• Fluorescent Peptides Labeled with Environment-Sensitive 7-Aminocoumarins and Their Interactions with Lipid Bilayer Membranes and Living Cells
  作者：Tokiko Murase、Toshitada Yoshihara、Keiichi Yamada、Seiji Tobita

  DOI：10.1246/bcsj.20120314

  日期：2013.4.15

  The photophysical properties of protected nonnatural amino acids Boc–l-Dap(7DEAC)–OMe (7DEAC: 7-diethylaminocoumarin) and Boc–l-Dap(C343)–OMe (C343: coumarin 343) were investigated to evaluate the suitability of these amino acids as fluorescent units in peptide-based fluorescent biosensors. The absorption and fluorescence spectra of Boc–l-Dap(7DEAC)–OMe and Boc–l-Dap(C343)–OMe exhibited significant red shifts with increasing solvent polarity. The fluorescence quantum yield and lifetime of Boc–l-Dap(7DEAC)–OMe solutions decreased remarkably with increasing solvent polarity, whereas those of Boc–l-Dap(C343)–OMe were slightly affected by the solvent polarity. Fluorescent peptides H–Dap(7DEAC)–LLA–OMe (1), H–Dap(7DEAC)–KLA–OMe (2), and H–Dap(7DEAC)–ELA–OMe (3) labeled with environment-sensitive 7DEAC were synthesized to examine the interactions of these labeled peptides with lipid membranes and living cells. Neutral 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and anionic 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG) liposomes were used to investigate peptide–membrane interactions. Hydrophobic peptide 1 exhibited high affinities to both DMPC and DMPC/DMPG mixed membranes. Of the three peptides, cationic peptide 2 exhibited the strongest affinity to DMPC/DMPG membranes, whereas anionic peptide 3 showed a much lower affinity to DMPC/DMPG membranes. These results could be interpreted based on hydrophobic and electrostatic interactions between the peptides and membranes. Peptide 1 was efficiently internalized into HeLa cells, whereas peptides 2 and 3 showed a much lower intracellular delivery.

  研究了受保护的非天然氨基酸Boc–l-Dap(7DEAC)–OMe (7DEAC: 7-二乙基氨基香豆素)和Boc–l-Dap(C343)–OMe (C343: 香豆素343)的光物理性质,以评估这些氨基酸作为肽基荧光生物传感器的荧光单元的适用性。Boc–l-Dap(7DEAC)–OMe和Boc–l-Dap(C343)–OMe的吸收和荧光光谱随着溶剂极性的增加呈现出显著的红移。Boc–l-Dap(7DEAC)–OMe溶液的荧光量子产率和寿命随着溶剂极性的增加显著降低,而Boc–l-Dap(C343)–OMe的荧光量子产率和寿命受溶剂极性的影响较小。合成了标记有环境敏感的7DEAC的荧光肽H–Dap(7DEAC)–LLA–OMe (1)、H–Dap(7DEAC)–KLA–OMe (2)和H–Dap(7DEAC)–ELA–OMe (3),以检查这些标记肽与脂质膜和活细胞的相互作用。使用中性的1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱(DMPC)和阴离子的1,2-二肉豆蔻酰-sn-甘油-3-[磷酸-rac-(1-甘油)] (DMPG)脂质体来研究肽-膜相互作用。疏水性肽1对DMPC和DMPC/DMPG混合膜表现出高亲和力。在这三种肽中,阳离子肽2对DMPC/DMPG膜表现出最强的亲和力,而阴离子肽3对DMPC/DMPG膜的亲和力要低得多。这些结果可以根据肽和膜之间的疏水性和静电相互作用来解释。肽1被有效地内化到HeLA细胞中,而肽2和3的细胞内递送要低得多。
• Phosphono Bisbenzguanidines as Irreversible Dipeptidomimetic Inhibitors and Activity-Based Probes of Matriptase-2
  作者：Daniela Häußler、Martin Mangold、Norbert Furtmann、Annett Braune、Michael Blaut、Jürgen Bajorath、Marit Stirnberg、Michael Gütschow

  DOI：10.1002/chem.201600206

  日期：2016.6.13

  present study, synthetic routes to nine dipeptidomimetic inactivators were developed. Five active compounds (41–45) were identified and characterized kinetically as irreversible inhibitors of matriptase‐2. In addition to a phosphonate warhead, these dipeptides possess two benzguanidine moieties as arginine mimetics to provide affinity for matriptase‐2 by binding to the S1 and S3/S4 subpockets, respectively

  Matriptase-2是一种II型跨膜丝氨酸蛋白酶，在人体内铁稳态中起关键作用。抑制matriptase-2被认为是治疗铁超负荷疾病（如血色素沉着症和β-地中海贫血）的一种有吸引力的策略。在本研究中，开发了九种二肽模拟物灭活剂的合成途径。鉴定出了五种活性化合物（41 – 45），并在动力学上鉴定为不可逆的matriptase-2抑制剂。除了膦酸酯战斗部外，这些二肽还具有两个作为精氨酸模拟物的苄胍基团，分别通过与S1和S3 / S4亚型结合，提供了对matriptase-2的亲和力。共价对接分析强烈支持这种结合模式。化合物41 –获得45种为两种非对映异构体的混合物，因此被分离为单一的差向异构体。化合物45 A在N末端氨基酸处具有S构型，在膦酸酯碳原子上具有R构型，是最有效的matriptase-2失活剂，失活速率常数为2790  m -1  s -1，并消除了完整细胞表面的膜结合型mat