Fmoc-L-hSer(Bzl)-OH | 1185841-92-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-L-hSer(Bzl)-OH
• 英文别名: Fmoc-Hse(Bzl)-OH；N-(((9H-Fluoren-9-yl)methoxy)carbonyl)-O-benzyl-L-homoserine；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-phenylmethoxybutanoic acid
• CAS: 1185841-92-2
• 化学式: C₂₆H₂₅NO₅
• 分子量: 431.488
• InChiKey: IYYLJDCIQNUTTJ-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332

反应信息

• 作为反应物：
  描述：

  Fmoc-L-hSer(Bzl)-OH 、 [7-(9H-芴-9-基甲氧基羰基氨基)-2-氧代-2H-色烯-4-基]-乙酸 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成
  参考文献：
  名称：

  A remarkable activity of human leukotriene A4 hydrolase (LTA4H) toward unnatural amino acids

  摘要：

  Leukotriene A(4) hydrolase (LTA4H--EC 3.3.2.6) is a bifunctional zinc metalloenzyme, which processes LTA(4) through an epoxide hydrolase activity and is also able to trim one amino acid at a time from N-terminal peptidic substrates via its aminopeptidase activity. In this report, we have utilized a library of 130 individual proteinogenic and unnatural amino acid fluorogenic substrates to determine the aminopeptidase specificity of this enzyme. We have found that the best proteinogenic amino acid recognized by LTA4H is arginine. However, we have also observed several unnatural amino acids, which were significantly better in terms of cleavage rate (k (cat)/K (m) values). Among them, the benzyl ester of aspartic acid exhibited a k (cat)/K (m) value that was more than two orders of magnitude higher (1.75 x 10(5) M-1 s(-1)) as compared to l-Arg (1.5 x 10(3) M-1 s(-1)). This information can be used for design of potent inhibitors of this enzyme, but may also suggest yet undiscovered functions or specificities of LTA4H.

  DOI：

  10.1007/s00726-014-1694-2
• 作为产物：
  描述：

  、 、 Fmoc-L-天冬氨酸 、 、 、 硼氢化钠 、 、 、 溴甲苯 以to give Fmoc-Homoserine benzyl ether α tert-butyl ester (43)的产率得到Fmoc-L-hSer(Bzl)-OH
  参考文献：
  名称：

  Peptidic Constructs with Amino Acid Surrogates

  摘要：

  含有至少一个环限制性氨基酸替代物I的肽构建物，其中R1、R2、R3、R4、R5、R6a、R6b、R7和y如规范中定义，以及多个氨基酸残基。

  公开号：

  US20110263818A1

文献信息

• Selective Substrates and Activity-Based Probes for Imaging of the Human Constitutive 20S Proteasome in Cells and Blood Samples
  作者：Wioletta Rut、Marcin Poręba、Paulina Kasperkiewicz、Scott J. Snipas、Marcin Drąg

  DOI：10.1021/acs.jmedchem.8b00026

  日期：2018.6.28

  the HyCoSuL approach, we designed and synthesized novel and selective fluorogenic substrates for each of these three constitutive 20S proteasome activities and applied them to assess inhibition of proteasome subunits by MG-132 and a clinically used inhibitor bortezomib. Our results confirm the utility of designed substrates in biochemical assays. Furthermore, selective peptide sequences obtained in this

  蛋白酶体是维持蛋白质稳态的关键酶复合物。蛋白酶体功能紊乱导致包括癌症，自身免疫和神经退行性疾病在内的病理。因此，蛋白酶体构成药物开发的极好的分子靶标。在这里，我们使用HyCoSuL方法为这三个20S组成型蛋白酶体活性中的每一个设计和合成了新颖的选择性荧光底物，并将它们应用于评估MG-132和临床使用的硼替佐米对蛋白酶体亚基的抑制作用。我们的结果证实了设计的底物在生化分析中的实用性。此外，以此方式获得的选择性肽序列用于构建荧光团标记的基于活性的探针，然后用于同时检测HEK-293F细胞和红细胞裂解液中的每个20S组成型蛋白酶体亚基。总体而言，我们描述了一种简单而快速的方法，可用于测量全血样本中20S组成型蛋白酶体的活性，该方法可以早期诊断与异常上调的蛋白酶体活性有关的病理状态。
• Design of Optical‐Imaging Probes by Screening of Diverse Substrate Libraries Directly in Disease‐Tissue Extracts
  作者：Martina Tholen、Joshua J. Yim、Katarzyna Groborz、Euna Yoo、Brock A. Martin、Nynke S. Berg、Marcin Drag、Matthew Bogyo

  DOI：10.1002/anie.202006719

  日期：2020.10.19

  an alternate, unbiased activity‐profiling approach in which whole tissue extracts are used to directly identify optimal peptide sequences for probe design. Screening of tumor extracts with a hybrid combinatorial substrate library (HyCoSuL) identified a combination of natural and non‐natural amino‐acid residues that was used to generate highly efficient tumor‐specific probes. This new strategy simplifies

  在癌症微环境中特异性激活的荧光淬灭探针在诊断、早期检测和手术指导方面具有巨大的潜在应用。这些探针通常设计为通过使用单一纯化酶直接优化来靶向与疾病相关的特定酶。然而，这可能会导致艰苦的化学努力，以产生在体内应用时性能欠佳的探针。我们在此描述了一种替代的、无偏的活性分析方法，其中使用全组织提取物直接鉴定用于探针设计的最佳肽序列。使用混合组合底物文库 (HyCoSuL) 筛选肿瘤提取物确定了天然和非天然氨基酸残基的组合，可用于生成高效的肿瘤特异性探针。
• A remarkable activity of human leukotriene A4 hydrolase (LTA4H) toward unnatural amino acids
  作者：Anna Byzia、Jesper Z. Haeggström、Guy S. Salvesen、Marcin Drag

  DOI：10.1007/s00726-014-1694-2

  日期：2014.5

  Leukotriene A(4) hydrolase (LTA4H--EC 3.3.2.6) is a bifunctional zinc metalloenzyme, which processes LTA(4) through an epoxide hydrolase activity and is also able to trim one amino acid at a time from N-terminal peptidic substrates via its aminopeptidase activity. In this report, we have utilized a library of 130 individual proteinogenic and unnatural amino acid fluorogenic substrates to determine the aminopeptidase specificity of this enzyme. We have found that the best proteinogenic amino acid recognized by LTA4H is arginine. However, we have also observed several unnatural amino acids, which were significantly better in terms of cleavage rate (k (cat)/K (m) values). Among them, the benzyl ester of aspartic acid exhibited a k (cat)/K (m) value that was more than two orders of magnitude higher (1.75 x 10(5) M-1 s(-1)) as compared to l-Arg (1.5 x 10(3) M-1 s(-1)). This information can be used for design of potent inhibitors of this enzyme, but may also suggest yet undiscovered functions or specificities of LTA4H.
• Peptidic Constructs with Amino Acid Surrogates
  申请人：SHARMA SHUBH D.

  公开号：US20110263818A1

  公开（公告）日：2011-10-27

  Peptidic constructs including at least one ring-constrained amino acid surrogate of formula I: where R 1 , R 2 , R 3 , R 4 , R 5 , R 6a , R 6b , R 7 , and y are as defined in the specification, and a plurality of amino acid residues.

  含有至少一个环限制性氨基酸替代物I的肽构建物，其中R1、R2、R3、R4、R5、R6a、R6b、R7和y如规范中定义，以及多个氨基酸残基。