(S)-(9H-fluoren-9-yl) methyl(1-hydroxy-5-(3-((2,2,4,6,7-pentamethyl-2,3 dihydrobenzofuran-5-yl)sulfonyl)guanidino)pentan-2-yl)carbamate | 260450-75-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-(9H-fluoren-9-yl) methyl(1-hydroxy-5-(3-((2,2,4,6,7-pentamethyl-2,3 dihydrobenzofuran-5-yl)sulfonyl)guanidino)pentan-2-yl)carbamate
• 英文别名: Fmoc-Arg(pbf)-OL；9H-fluoren-9-ylmethyl N-[(2S)-5-[[amino-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]-1-hydroxypentan-2-yl]carbamate
• CAS: 260450-75-7
• 化学式: C₃₄H₄₂N₄O₆S
• 分子量: 634.797
• InChiKey: OCIHRKILVJXVGL-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-(9H-fluoren-9-yl) methyl(1-hydroxy-5-(3-((2,2,4,6,7-pentamethyl-2,3 dihydrobenzofuran-5-yl)sulfonyl)guanidino)pentan-2-yl)carbamate 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 、 水 为溶剂， 以85%的产率得到Fmoc-Arg(Pbf)-H
  参考文献：
  名称：

  A Peptide Aldehyde Microarray for High-Throughput Profiling of Cellular Events

  摘要：

  Microarrays provide exciting opportunities in the field of large-scale proteomics. With the aim to elucidate enzymatic activity and profiles within native biological samples, we developed a microarray comprising a focused positional-scanning library of enzyme inhibitors. The library was diversified across P-1-P-4 positions, creating 270 different inhibitor sublibraries which were immobilized onto avidin slides. The peptide aldehyde-based small-molecule microarray (SMM) specifically targeted cysteine proteases, thereby enabling large-scale functional assessment of this subgroup of proteases, within fluorescently labeled samples, including pure proteins, cellular lysates, and infected samples. The arrays were shown to elicit binding fingerprints consistent with those of model proteins, specifically caspases and purified cysteine proteases from parasites (rhodesein and cruzain). When tested against lysates from apoptotic Hela and red blood cells infected with Plasmodium falciparum, clear signatures were obtained that were readily attributable to the activity of constituent proteases within these samples. Characteristic binding profiles were further able to distinguish various stages of the parasite infection in erythrocyte lysates. By converting one of our brightest microarray hits into a probe, putative protein markers were identified and pulled down from within apoptotic Hela lysates, demonstrating the potential of target validation and discovery. Taken together, these results demonstrate the utility of targeted SMMs in dissecting cellular biology in complex proteomic samples.

  DOI：

  10.1021/ja109597v
• 作为产物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.25h， 以0.8 g的产率得到(S)-(9H-fluoren-9-yl) methyl(1-hydroxy-5-(3-((2,2,4,6,7-pentamethyl-2,3 dihydrobenzofuran-5-yl)sulfonyl)guanidino)pentan-2-yl)carbamate
  参考文献：
  名称：

  C-Terminal Modifications Broaden Activity of the Proline-Rich Antimicrobial Peptide, Chex1-Arg20

  摘要：

  利用 Fmoc/tBu 固相肽合成技术，通过不同的化学策略获得了一系列富含脯氨酸的单体抗菌肽 Chex1-Arg20 的 N 端和 C 端修饰，以研究它们对一系列革兰氏阴性细菌的作用。特别是在 C 端用酰肼或醇功能修饰后，它们的抗菌活性从大肠杆菌和肺炎双球菌扩展到了其他革兰氏阴性菌、鲍曼不动杆菌和铜绿假单胞菌。此外，这些类似物对哺乳动物细胞没有细胞毒性。因此，与母肽相比，这种修饰可能有助于开发对革兰氏阴性菌具有更强活性谱的富脯氨酸抗菌肽。

  DOI：

  10.1071/ch15169

文献信息

• Mild and Efficient Synthesis of Fmoc-Protected Amino Azides from Fmoc-Protected Amino Alcohols
  作者：Erkang Fan、Somnath Mondal

  DOI：10.1055/s-2005-923589

  日期：——

  Fmoc-protected amino azides - key intermediates for monomers of oligomeric urea and guanidine - can be efficiently prepared from the corresponding amino alcohol through iodination followed by substitution with sodium azide. This synthetic route avoids the preparation, storage, and handling of the highly toxic azidic acid that is used in an alternative method.

  Fmoc保护的氨基叠氮化物 - 聚氨基脲和胍的单体关键中间体 - 可以通过碘化和随后用叠氮化钠取代的方法，从相应的氨基醇高效制备。该合成路线避免了在另一种方法中制备、储存和处理高度毒性的叠氮酸。
• Structural Basis for α‐Helix Mimicry and Inhibition of Protein–Protein Interactions with Oligourea Foldamers
  作者：Léonie Cussol、Laura Mauran‐Ambrosino、Jérémie Buratto、Anna Y Belorusova、Maxime Neuville、Judit Osz、Sébastien Fribourg、Juliette Fremaux、Christel Dolain、Sébastien R. Goudreau、Natacha Rochel、Gilles Guichard

  DOI：10.1002/anie.202008992

  日期：2021.2

  different options, foldamers, which are sequence‐based oligomers with precise folded conformation, have emerged as a promising technology. We introduce oligourea foldamers to reduce the peptide character of inhibitors of protein–protein interactions (PPI). However, the precise design of such mimics is currently limited by the lack of structural information on how these foldamers adapt to protein surfaces

  有效地优化肽导入候选药物的过程经常需要进一步改造，以增强诸如生物利用度的特性。在不同的选择中，折叠子是具有前景的技术，它是具有精确折叠构象的基于序列的寡聚物。我们引入低聚尿素折叠剂以减少蛋白质-蛋白质相互作用（PPI）抑制剂的肽特征。然而，由于缺乏关于这些折叠物如何适应蛋白质表面的结构信息，目前这种模拟物的精确设计受到限制。我们报道了与寡聚体连接酶MDM2和维生素D受体复合的肽-寡聚尿素杂种的X射线结构，并显示了如何设计这种杂合寡聚体以高亲和力结合蛋白质靶标。
• Urea moiety as amide bond mimetic in peptide-like inhibitors of VEGF-A165/NRP-1 complex
  作者：Anna K. Puszko、Piotr Sosnowski、Karolina Pułka-Ziach、Olivier Hermine、Gérard Hopfgartner、Yves Lepelletier、Aleksandra Misicka

  DOI：10.1016/j.bmcl.2019.07.016

  日期：2019.9

  NRP-1 is an important co-receptor of vascular endothelial growth factor receptor-2 (VEGFR-2). Many reports suggested that NRP-1 might also serve as a separate receptor for VEGF-A(165) causing stimulation of tumour growth and metastasis. Therefore, compounds interfering with VEGF-A(165)/NRP-1 complex triggered interest in the design of new molecules, including peptides, as anti-angiogenic and anti-tumour drugs. Here, we report the synthesis, affinity and stability evaluation of the urea-peptide hybrids, based on general Lys(hArg)-AA(2)-AA(3)-Arg sequence, where hArg residue was substituted by Arg urea unit. Such substitution does not substantially affected affinity of compounds for NRP-1 but significantly increased their proteolytic stability in plasma.