Fmoc-D-Glu(OtBu)-H | 1082742-43-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-D-Glu(OtBu)-H
• 英文别名: Fmoc-D-Glu(OBut)-Wang Resin (100-200mesh, 1% DVB)；tert-butyl (4R)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-5-oxopentanoate
• CAS: 1082742-43-5
• 化学式: C₂₄H₂₇NO₅
• 分子量: 409.482
• InChiKey: BCIPGSZQUDLGSY-MRXNPFEDSA-N

物化性质

• 沸点：
  582.5±50.0 °C(Predicted)
• 密度：
  1.176±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Fmoc-D-Glu(OtBu)-H 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.17h， 生成 (R)-N-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-(tertbutoxy)-5-oxopentyl)-N-(methylsulfonyl)glycine
  参考文献：
  名称：

  作为蛋白质-蛋白质相互作用的强效抑制剂的右手 d-Sulfono-γ-AApeptide 螺旋折叠体的合理设计和合成。

  摘要：

  已经有效地设计和合成了前所未有的新型螺旋折叠器。均质右旋d-磺基-γ-AApeptides代表了新一代非天然螺旋肽模拟物，其具有与α-肽相似的折叠构象，使其成为设计α-螺旋模拟物的理想分子支架。正如 p53-MDM2 PPI 作为模型应用所证明的那样，与 p53 肽相比，右手d-磺基-γ-AApeptides 显示出大大增强的结合亲和力。d-磺基-γ-AApeptides的设计可能为调节蛋白质-蛋白质相互作用提供一种新的替代策略。

  DOI：

  10.1021/acs.joc.0c00996
• 作为产物：
  描述：

  N-芴甲氧羰基-D-谷氨酸 gamma-叔丁酯 在 N-甲基吗啉 、 甲醇 、 sodium tetrahydroborate 、 草酰氯 、 二甲基亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 1.08h， 生成 Fmoc-D-Glu(OtBu)-H
  参考文献：
  名称：

  Triazolo-Peptidomimetics：新型放射性标记的Minigastrin类似物，可改善肿瘤靶向性。

  摘要：

  MG11是minigastrin的截短类似物，minigastrin是一种对胆囊收缩素2受体（CCK2R）具有高亲和力和特异性的肽，在不同的肿瘤中过表达。因此，放射性标记的MG11衍生物具有用于癌症诊断和治疗的巨大潜力。MG11的一个缺点是它可以被蛋白酶快速降解，从而导致体内中等程度的肿瘤吸收。我们引入了1,4-二取代的1,2,3-三唑作为代谢稳定的生物等排体，以取代该肽的不稳定酰胺键。“三唑扫描”产生的拟肽具有改善的对酶促降解的抗性和/或对CCK2R的亲和力。值得注意的是，我们的先导化合物的受体亲和力提高了10倍，导致体内肿瘤吸收提高了2.6倍。配体-CCK2R络合物的模型表明，芳香三唑部分与受体的Arg356残基的额外阳离子-π相互作用是造成这些现象的原因。我们首次展示了酰胺基至三唑的取代策略为药物开发提供了新的机遇，其超越了生物活性肽的代谢稳定性。

  DOI：

  10.1021/acs.jmedchem.9b01936

文献信息

• DNA-Templated Polymerization of Side-Chain-Functionalized Peptide Nucleic Acid Aldehydes
  作者：Ralph E. Kleiner、Yevgeny Brudno、Michael E. Birnbaum、David R. Liu

  DOI：10.1021/ja0753997

  日期：2008.4.1

  The DNA-templated polymerization of synthetic building blocks provides a potential route to the laboratory evolution of sequence-defined polymers with structures and properties not necessarily limited to those of natural biopolymers. We previously reported the efficient and sequence-specific DNA-templated polymerization of peptide nucleic acid (PNA) aldehydes. Here, we report the enzyme-free, DNA-templated polymerization of side-chain-functionalized PNA tetramer and pentamer aldehydes. We observed that polymerization of tetramer and pentamer PNA building blocks with a single lysine-based side chain at various positions in the building block could proceed efficiently and sequence specifically. In addition, DNA-templated polymerization also proceeded efficiently and in a sequence-specific manner with pentamer PNA aldehydes containing two or three lysine side chains in a single building block to generate more densely functionalized polymers. To further our understanding of side-chain compatibility and expand the capabilities of this system, we also examined the polymerization efficiencies of 20 pentamer building blocks each containing one of five different side-chain groups and four different side-chain regio- and stereochemistries. Polymerization reactions were efficient for all five different side-chain groups and for three of the four combinations of side-chain regio- and stereochemistries. Differences in the efficiency and initial rate of polymerization correlate with the apparent melting temperature of each building block, which is dependent on side-chain regio- and stereochemistry but relatively insensitive to side-chain structure among the substrates tested. Our findings represent a significant step toward the evolution of sequence-defined synthetic polymers and also demonstrate that enzyme-free nucleic acid-templated polymerization can occur efficiently using substrates with a wide range of side-chain structures, functionalization positions within each building block, and functionalization densities.
• N-Acylpolyamine inhibitors of HDM2 and HDMX binding to p53
  作者：Ryo Hayashi、Deyun Wang、Toshiaki Hara、Jaclyn A. Iera、Stewart R. Durell、Daniel H. Appella

  DOI：10.1016/j.bmc.2009.10.032

  日期：2009.12

  Selective inhibition of protein-protein interactions important for cellular processes could lead to the development of new therapies against disease. In the area of cancer, overexpression of the proteins human double minute 2 (HDM2) and its homolog HDMX has been linked to tumor aggressiveness. Both HDM2 and HDMX bind to p53 and prevent cell cycle arrest or apoptosis in damaged cells. Developing a strategy to simultaneously prevent the binding of both HDM2 and HDMX to p53 is an essential feature of inhibitors to restore p53 activity in a number of different cancers. Inhibition of protein-protein interactions with synthetic molecules is an emerging area of research that requires new inhibitors tailored to mimic the types of interfaces between proteins. Our strategy to create inhibitors of protein-protein interactions is to develop a non-natural scaffold that may be used as a starting point to identify important molecular components necessary for inhibition. In this study, we report an N-acylpolyamine (NAPA) scaffold that supports numerous sidechains in a compact atomic arrangement. NAPAs were constructed by a series of reductive aminations between amino acid derivatives followed by acylation at the resulting secondary amine. An optimized NAPA was able to equally inhibit the association of both HDM2 and HDMX with p53. Our results demonstrate some of the challenges associated with targeting multiple protein-protein interactions involved in overlapping cellular processes. Published by Elsevier Ltd.
• Synthesis of Enantiopure γ-Glutamic Acid Functionalized Peptide Nucleic Acid Monomers
  作者：Hu Huang、Goon-Ho Joe、Sung-Rok Choi、Su-Nam Kim、Yong-Tae Kim、Chwang-Siek Pak、Joon-Hee Hong、Won-Jae Lee

  DOI：10.5012/bkcs.2010.31.7.2054

  日期：2010.7.20