N-FMOC-6-苄氧基-L-正亮氨酸 | 625845-42-3

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N-FMOC-6-苄氧基-L-正亮氨酸
• 英文名称: (S)-6-Benzyloxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid
• 英文别名: Fmoc-L-Nle(6-OBzl)-OH；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-phenylmethoxyhexanoic acid
• CAS: 625845-42-3
• 化学式: C₂₈H₂₉NO₅
• 分子量: 459.542
• InChiKey: KMQPPEZRVRMLME-SANMLTNESA-N

物化性质

• 沸点：
  671.6±55.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-FMOC-6-苄氧基-L-正亮氨酸 、 [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

文献信息

• Unnatural amino acids increase sensitivity and provide for the design of highly selective caspase substrates
  作者：M Poreba、P Kasperkiewicz、S J Snipas、D Fasci、G S Salvesen、M Drag

  DOI：10.1038/cdd.2014.64

  日期：2014.9

  proteases - the human caspases. The power of this library for caspase discrimination extends far beyond traditional PS-SCL approach, as in addition to 19 natural amino acids we also used 110 diverse unnatural amino acids that can more extensively explore the chemical space represented by caspase-active sites. Using this approach we identified and employed peptide-based substrates that provided excellent

  传统的组合肽基底物库方法通常利用天然氨基酸，限制了该工具在为具有相似底物特异性特征的蛋白酶生成选择性底物方面的用途。为了解决这个限制，我们合成了一个具有 Ac-P4-P3-P2-Asp-ACC 通式的混合组合底物库 (HyCoSuL)，在一个密切相关的蛋白酶家族 - 人类半胱天冬酶上测试了该方法。这个库用于 caspase 区分的能力远远超出了传统的 PS-SCL 方法，因为除了 19 种天然氨基酸之外，我们还使用了 110 种不同的非天然氨基酸，可以更广泛地探索由 caspase 活性位点表示的化学空间。
• Peptide compounds and their use as protease substrates
  申请人：——

  公开号：US20040018561A1

  公开（公告）日：2004-01-29

  This invention is directed generally to peptide compounds and salts, and particularly to peptide compounds and salts that are useful as protease substrates, such as matrix metalloprotease (“MMP”) substrates. This invention also is directed to methods for making such compounds and salts, as well as amino acids that may, for example, be used in such methods. This invention is further directed to methods for using such compounds and salts to, for example, evaluate the effectiveness of potential protease inhibitors and to detect or monitor a disease associated with protease activity.

  该发明通常涉及肽化合物和盐，特别是肽化合物和盐，它们可作为蛋白酶底物，例如基质金属蛋白酶（“MMP”）底物。该发明还涉及制备这类化合物和盐的方法，以及可能用于这类方法中的氨基酸。该发明还进一步涉及使用这类化合物和盐的方法，例如用于评估潜在的蛋白酶抑制剂的有效性，以及检测或监测与蛋白酶活性相关的疾病。
• Heterocyclic pyrazole-carboxamidesas P2Y12 antagonists
  申请人：Nazaré Marc

  公开号：US08426420B2

  公开（公告）日：2013-04-23

  The present invention relates to compounds of the formula I, wherein R1; R2; Z; A; B; D; Q; J; V; G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong anti-aggregating effect on platelets and thus an anti-thrombotic effect and are suitable, e.g., for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible antagonists of the platelet ADP receptor P2Y12, and can in general be applied in conditions in which an undesired activation of the platelet ADP receptor P2Y12 is present or for the cure or prevention of which an inhibition of the platelet ADP receptor P2Y12 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及式I的化合物，其中R1; R2; Z; A; B; D; Q; J; V; G和M具有声明中指示的含义。式I的化合物是有价值的药理活性化合物。它们表现出强烈的抗血小板聚集作用，因此具有抗血栓作用，适用于治疗和预防心血管疾病，如血栓栓塞性疾病或再狭窄。它们是血小板ADP受体P2Y12的可逆拮抗剂，通常可应用于存在血小板ADP受体P2Y12的不良激活或预防其抑制的情况的治疗或预防。本发明还涉及制备式I化合物的过程，它们的使用，特别是作为药物中的活性成分，以及包含它们的制药制剂。
• HETEROCYCLIC PYRAZOLE-CARBOXAMIDESAS P2Y12 ANTAGONISTS
  申请人：Nazaré Marc

  公开号：US20110021537A1

  公开（公告）日：2011-01-27

  The present invention relates to compounds of the formula I, wherein R1; R2; Z; A; B; D; Q; J; V; G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong anti-aggregating effect on platelets and thus an anti-thrombotic effect and are suitable, e.g., for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible antagonists of the platelet ADP receptor P2Y12, and can in general be applied in conditions in which an undesired activation of the platelet ADP receptor P2Y12 is present or for the cure or prevention of which an inhibition of the platelet ADP receptor P2Y12 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及式I的化合物，其中R1；R2；Z；A；B；D；Q；J；V；G和M具有所述声明中指示的含义。式I的化合物是有价值的药理活性化合物。它们对血小板具有强烈的抗聚集作用，因此具有抗血栓作用，适用于治疗和预防心血管疾病，如血栓栓塞性疾病或再狭窄。它们是血小板ADP受体P2Y12的可逆拮抗剂，并且通常适用于存在不希望的血小板ADP受体P2Y12激活的情况，或者用于治疗或预防需要抑制血小板ADP受体P2Y12的情况。此外，本发明还涉及式I化合物的制备方法，它们的用途，特别是作为药物中的活性成分，以及包含它们的制剂。
• Toolbox of Fluorescent Probes for Parallel Imaging Reveals Uneven Location of Serine Proteases in Neutrophils
  作者：Paulina Kasperkiewicz、Yoav Altman、Maximiliano D’Angelo、Guy S. Salvesen、Marcin Drag

  DOI：10.1021/jacs.7b04394

  日期：2017.7.26

  Neutrophils, the front line defenders against infection, express four serine proteases (NSPs) that play roles in the control of cell-signaling pathways and defense against pathogens and whose imbalance leads to pathological conditions. Dissecting the roles of individual NSPs in humans is problematic because neutrophils are end-stage cells with a short half-life and minimal ongoing protein synthesis. To gain insight into the regulation of NSP activity we have generated a small-molecule chemical toolbox consisting of activity-based probes with different fluorophore-detecting groups with minimal wavelength overlap and highly selective natural and unnatural amino acid recognition sequences. The key feature of these activity-based probes is the ability to use them for simultaneous observation and detection of all four individual NSPs by fluorescence microscopy, a feature never achieved in previous studies. Using these probes we demonstrate uneven distribution of NSPs in neutrophil azurophil granules, such that they seem to be mutually excluded from each other, suggesting the existence of unknown granule-targeting mechanisms.