N²-(((9H-fluoren-9-yl)methoxy)carbonyl)-N⁴-methyl-L-asparagine | 149204-93-3

• 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: N²-(((9H-fluoren-9-yl)methoxy)carbonyl)-N⁴-methyl-L-asparagine
• 英文别名: Fmoc-Asn(Me)-COOH；n-Fmoc-n'-methyl-l-asparagine；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-(methylamino)-4-oxobutanoic acid
• CAS: 149204-93-3
• 化学式: C₂₀H₂₀N₂O₅
• 分子量: 368.389
• InChiKey: GCQNMZCRYMMHTM-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P301+P312,P302+P352,P304+P340,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N²-(((9H-fluoren-9-yl)methoxy)carbonyl)-N⁴-methyl-L-asparagine 、 1,3,5-三(氨基甲基)-2,4,6-三乙基苯 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  A Colorimetric Sensing Ensemble for Heparin

  摘要：

  A receptor possessing ammoniums and a novel amino acid with a boronic acid side chain was designed and synthesized. The receptor shows good affinity and selectivity for heparin over similar polysaccharides possessing lower anionic charge density. The affinity for heparin is similar to that for a heparin disaccharide, indicating that disaccharidic units are the likely sites for binding to the receptor. The receptor has a potential use for creating a colorimetric assay for heparin.

  DOI：

  10.1021/ja020505k
• 作为产物：
  描述：

  芴甲氧羰基-L-天冬氨酸-1-叔丁酯 在 1-羟基苯并三唑 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 N²-(((9H-fluoren-9-yl)methoxy)carbonyl)-N⁴-methyl-L-asparagine
  参考文献：
  名称：

  A Colorimetric Sensing Ensemble for Heparin

  摘要：

  A receptor possessing ammoniums and a novel amino acid with a boronic acid side chain was designed and synthesized. The receptor shows good affinity and selectivity for heparin over similar polysaccharides possessing lower anionic charge density. The affinity for heparin is similar to that for a heparin disaccharide, indicating that disaccharidic units are the likely sites for binding to the receptor. The receptor has a potential use for creating a colorimetric assay for heparin.

  DOI：

  10.1021/ja020505k

文献信息

• <i>N</i>^γ‐Hydroxyasparagine: A Multifunctional Unnatural Amino Acid That is a Good P1 Substrate of Asparaginyl Peptide Ligases
  作者：Yiyin Xia、Janet To、Ning‐Yu Chan、Side Hu、Heng Tai Liew、Seetharamsing Balamkundu、Xiaohong Zhang、Julien Lescar、Surajit Bhattacharjya、James P. Tam、Chuan‐Fa Liu

  DOI：10.1002/anie.202108125

  日期：2021.10.4

  hyperstable tetracyclic scaffold of rhesus theta defensin-1. The Asn(OH) residue in the cyclized peptides can also be readily oxidized to Asp. By this approach, we synthesized several bioactive Asp-containing cyclic peptides (MCoTI-II, kB2, SFTI, and integrin-targeting RGD peptides) that are otherwise difficult targets for PAL-catalyzed cyclization owing to unfavorable kinetics of the P1-Asp substrates. This

  肽基天冬酰胺基连接酶 (PAL) 是肽大环化的有力工具。在此，我们报告了 Asn 的衍生物，即N γ -羟基天冬酰胺或 Asn(OH)，是 PAL 的非天然 P1 底物。通过 Asn(OH) 介导的环化，我们制备了环肽作为新的基质金属蛋白酶 2 (MMP2) 抑制剂，显示 Asn(OH) 的异羟肟酸部分作为关键药效团。最有效的环肽（K i=2.8±0.5 nM) 建立在恒河猴 theta defensin-1 的超稳定四环支架上。环化肽中的 Asn(OH) 残基也很容易被氧化成 Asp。通过这种方法，我们合成了几种含有生物活性 Asp 的环肽（MCoTI-II、kB2、SFTI 和靶向整合素的 RGD 肽），由于 P1-Asp 底物的不利动力学，这些环肽是 PAL 催化环化的困难目标。这项研究表明，底物工程是一种有用的策略，可以扩大 PAL 连接在治疗性环肽合成中的应用。
• [EN] METHODS FOR CYCLIZATION OF (POLY)PEPTIDES COMPRISING Nγ-HYDROXY- OR Nγ-AMINO-L-ASPARAGINE<br/>[FR] PROCÉDÉS DE CYCLIZATION DE (POLY)PEPTIDES COMPRENANT DE LA Nγ-HYDROXY- OU Nγ-AMINO-L-ASPARAGINE
  申请人：UNIV NANYANG TECH

  公开号：WO2022186782A1

  公开（公告）日：2022-09-09

  The present invention relates to methods that employ enzymes having Asn-specific cyclase activity as a means for generating cyclic (poly)peptides from (poly)peptides that comprise a ligation motif comprising a Nγ-hydroxy-L-asparagine or Nγ-amino-L-asparagine residue. Further encompassed are the resulting cyclic (poly)peptides and the corresponding uses.

  本发明涉及使用具有Asn特异性环化酶活性的酶作为从包含连接基序的多肽中生成环状（多）肽的手段的方法。连接基序包括Nγ-羟基-L-天冬氨酸或Nγ-氨基-L-天冬氨酸残基。还包括所得到的环状（多）肽及其相应的用途。
• Structure–activity study at positions 3 and 4 of human neuropeptide S
  作者：Valeria Camarda、Claudio Trapella、Girolamo Calo’、Remo Guerrini、Anna Rizzi、Chiara Ruzza、Stella Fiorini、Erika Marzola、Rainer K. Reinscheid、Domenico Regoli、Severo Salvadori

  DOI：10.1016/j.bmc.2008.08.073

  日期：2008.10

  Neuropeptide S (NPS) has been identified as the endogenous ligand of a previously orphan receptor now named NPSR. Previous studies demonstrated that the N-terminal sequence Phe(2)-Arg(3)-Asn(4) of the peptide is crucial for biological activity. Here, we report on a focused structure-activity study of Arg(3) and Asn(4) that have been replaced with a series of coded and non-coded amino acids. Thirty-eight human NPS analogues were synthesized and pharmacologically tested for intracellular calcium mobilization using HEK293 cells stably expressing the mouse NPSR. The results of this study demonstrated the following NPS position 3 structure-activity features: (i) the guanidine moiety and its basic character are not crucial requirements, (ii) an aliphatic amino acid with a linear three carbon atom long side chain is sufficient to bind and fully activate NPSR, (iii) the receptor pocket allocating the position 3 side chain can accommodate slightly larger side chains at least to a certain degree [hArg, Arg(NO(2)) or Arg(Me)(2) but not Arg(Tos)]. Position 4 seems to be more sensitive to amino acids replacement compared to position 3; in fact, all the amino acid replacements investigated produced either an important decrease of biological activity or generated inactive derivatives suggesting a pivotal role of the Asn4 side chain for NPS bioactivity. (C) 2008 Elsevier Ltd. All rights reserved.
• A Colorimetric Sensing Ensemble for Heparin
  作者：Zhenlin Zhong、Eric V. Anslyn

  DOI：10.1021/ja020505k

  日期：2002.8.1

  A receptor possessing ammoniums and a novel amino acid with a boronic acid side chain was designed and synthesized. The receptor shows good affinity and selectivity for heparin over similar polysaccharides possessing lower anionic charge density. The affinity for heparin is similar to that for a heparin disaccharide, indicating that disaccharidic units are the likely sites for binding to the receptor. The receptor has a potential use for creating a colorimetric assay for heparin.