N-α-carbenzoxy-N-ε-methyl-L-lysine | 1001647-16-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-α-carbenzoxy-N-ε-methyl-L-lysine
• 英文别名: Z-Lys(me)-OH；(2S)-6-(methylamino)-2-(phenylmethoxycarbonylamino)hexanoic acid
• CAS: 1001647-16-0
• 化学式: C₁₅H₂₂N₂O₄
• 分子量: 294.351
• InChiKey: JQCTZFCWAPVQAV-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-α-carbenzoxy-N-ε-methyl-L-lysine 在 palladium on activated charcoal 盐酸 、 lithium hydroxide 、 氢气 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (8S,11R,12S)-11-Isobutyl-3-methyl-2,10-dioxo-1-oxa-3,9-diaza-cyclopentadecane-8,12-dicarboxylic acid 12-(benzyloxy-amide) 8-methylamide
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Macrocyclic Hydroxamic Acids That Inhibit Tumor Necrosis Factor α Release in Vitro and in Vivo

  摘要：

  To search for TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE) inhibitors, we designed a new class of macrocyclic hydroxamic acids by linking the PI and P2 ' residues of acyclic anti-succinate-based hydroxamic acids. A variety of residues including amide, carbamate, alkyl, sulfonamido, Boc-amino, and amino were found to be suitable P1-P2 ' linkers. With an N-methylamide at P3 ', the 13-16-membered macrocycles prepared exhibited low micromolar activities in the inhibition of TNF-alpha release from LPS-stimulated human whole blood. Further elaboration in the P3 ' -P4 ' area using the cyclophane and cyclic carbamate templates led to the identification of a number of potent analogues with IC50 values of less than or equal to 0.2 muM in whole blood assay (WBA). Although the P3 ' area can accommodate a broad array of structurally diversified functional groups including polar residues, hydrophobic residues, and amino and carboxylic acid moieties, in both the cyclophane series and the cyclic carbamate series, a glycine residue at P3 ' was identified as a critical structural component to achieve both good in vitro potency and good oral activity. With a glycine residue at P3 ', an N-methylamide at P4 ' provided the best cyclophane analogue, SL422 (WBA IC50 = 0.22 muM, LPS-mouse ED50 = 15 mg/kg, po), whereas a morpholinylamide at P4 ' afforded the most potent and most orally active cyclic carbamate analogue, SP057 (WBA IC50 = 0.067 muM, LPS-mouse ED50 = 2.3 mg/kg, po). Further profiling for SL422 and SP057 showed that these macrocyclic compounds are potent TACE inhibitors, with K-i values of 12 and 4.2 nM in the porcine TACE assay, and are broad-spectrum MMP inhibitors. Pharmacokinetic studies in beagle dogs revealed that SL422 and SP057 are orally bioavailable, with oral bioavailabilities of 11% and 23%, respectively.

  DOI：

  10.1021/jm010127e
• 作为产物：
  描述：

  N-alpha-Cbz-L-赖氨酸 在 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 N-α-carbenzoxy-N-ε-methyl-L-lysine
  参考文献：
  名称：

  通过 SN Ar 反应检测肽赖氨酸残基的 N-ε-单甲基化的选择性试剂

  摘要：

  组蛋白特定赖氨酸残基的甲基化由组蛋白甲基转移酶 (HMT) 催化，并在基因表达的表观遗传控制中起关键作用。已经建立了几种检测赖氨酸残基 Ne 甲基化的方法，以评估 HMT 的活性、开发抑制剂和鉴定底物。然而，它们大多使用特异性抗体或酶，如肽酶，其可靠性和重现性往往取决于蛋白质试剂的质量和反应条件。在这里，我们描述了一种通过简单的化学反应检测赖氨酸残基 Ne-单甲基化的便捷方法。我们专注于芳香亲电子试剂与伯氨基或单甲基化氨基之间的亲核芳香取代反应（SNAr 反应）。对各种亲电子试剂的筛选表明，4-氟-2-硝基苯乙酮 (1g) 对赖氨酸的 Ne-单甲基化氨基具有高选择性。此外，1g与赖氨酸和Ne-单甲基化赖氨酸的反应产物5g和6g分别显示出不同的吸收光谱，即6g在350nm处的吸光度是5g的13倍。我们表明 1g 的这些特征特性可用于选择性检测 HMT 底物肽中赖氨酸残基的甲基化状态，并用于检测

  DOI：

  10.1002/ejoc.201700488

文献信息

• Compounds and Compositions as Channel Activating Protease Inhibitors
  申请人：Tully C. David

  公开号：US20070275906A1

  公开（公告）日：2007-11-29

  The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for, using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.

  该发明提供了化合物及其制药组合物，用于调节通道激活蛋白酶，并使用这些化合物来治疗、改善或预防与通道激活蛋白酶相关的疾病的方法，包括但不限于前列腺蛋白酶、PRSS22、TMPRSS11（例如TMPRSS11B、TMPRSS11E）、TMPRSS2、TMPRSS3、TMPRSS4（MTSP-2）、麦曲蛋白酶（MTSP-1）、CAP2、CAP3、胰蛋白酶、卡特普辛A或中性粒细胞弹性蛋白酶。
• [EN] ALYSINE MONOMETHYLATED DERIVATIVE AND CORRESPONDING ANTIBODY AND USE THEREOF<br/>[FR] DÉRIVÉ MONOMÉTHYLÉ DE LA LYSINE, ANTICORPS CORRESPONDANT ET UTILISATION ASSOCIÉE
  申请人：PMT BIOLABS INC

  公开号：WO2016011920A1

  公开（公告）日：2016-01-28

  Provided are artificially synthesized modified mono-methylated lysines and modified mono-methylated lysine derivatized polypeptides. Also provided is an antibody produced by using this modified mono-methylated lysine and modified mono-methylated lysine derivatized polypeptide as an antigen, the antibody can be used in recognizing and enriching the modified polypeptide after the lysine mono-methylated polypeptide being derivatized in vitro. Also provided are a preparation method of said antibody, a method for identifying and quantifying the lysine mono-methylated modified substrate in cell or tissue by using proteomics approach of affinity enrichment for specific antibody and mass spectrometry.

  提供了人工合成的修饰的单甲基化赖氨酸和修饰的单甲基化赖氨酸衍生的多肽。还提供了一种通过使用这种修饰的单甲基化赖氨酸和修饰的单甲基化赖氨酸衍生的多肽作为抗原而产生的抗体，该抗体可用于在体外将赖氨酸单甲基化多肽衍生化后识别和富集修饰的多肽。还提供了该抗体的制备方法，以及通过亲和富集特异抗体和质谱法的蛋白质组学方法在细胞或组织中识别和定量赖氨酸单甲基化修饰底物的方法。
• Compounds for targeting drug delivery and enhancing siRNA activity
  申请人：Nitto Denko Corporation

  公开号：US10000447B2

  公开（公告）日：2018-06-19

  Here described are compounds consisting of the structure (targeting molecule)m-linker-(targeting molecule)n, wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including these compounds which are useful for the targeting and delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.

  这里描述的是由以下结构组成的化合物 (靶向分子）m-连接剂-（靶向分子）n、 其中，靶向分子是在靶细胞上具有特异性受体的视黄醇或脂溶性维生素；其中，m 和 n 独立地为 0、1、2 或 3；其中，连接剂包括聚乙二醇（PEG）或类 PEG 分子，以及包括这些化合物的组合物和药物制剂，这些组合物和药物制剂可用于治疗剂的靶向和递送；以及使用这些组合物和药物制剂的方法。
• COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTIVATING PROTEASE INHIBITORS
  申请人：Tully David C.

  公开号：US20110257077A1

  公开（公告）日：2011-10-20

  The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for, using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.
• US7951823B2
  申请人：——

  公开号：US7951823B2

  公开（公告）日：2011-05-31