N-α-acetyllysine amide | 19789-60-7

• 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: N-α-acetyllysine amide
• 英文别名: α-acetyl-L-lysinamide；N-acetyllysinamide；Ac-Lys-amide；Ac-Lys-NH2；Ac-Lys-NH₂；N^α-Acetyl-L-lysinamid；(S)-2-Acetamido-6-aminohexanamide；(2S)-2-acetamido-6-aminohexanamide
• CAS: 19789-60-7
• 化学式: C₈H₁₇N₃O₂
• 分子量: 187.242
• InChiKey: RXDBWNXJJIDFEF-ZETCQYMHSA-N

物化性质

• 熔点：
  134-138 °C
• 沸点：
  473.8±40.0 °C(Predicted)
• 密度：
  1.092±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  98.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-α-acetyllysine amide 、 4-硝基苯基乙酸酯 在 碳酸氢钠 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 21.0h， 生成 α,ε-diacetyl-L-lysinamide
  参考文献：
  名称：

  Examination of the aspirin acetylation site of human serum albumin by13C NMR spectroscopy

  摘要：

  AbstractHuman serum albumin has been specifically acetylated using aspirin in which the methyl carbon of the acetyl group was enriched to 90% 13C. A single resonance at 23.13 ppm downfield from tetramethylsilane was observed in 13C differences spectra obtained at both 25.2 and 45.3 MHz. Chemical shift studies of several model compounds suggest that this is the resonance position to be expected for an acetamide group exposed to solvent. The line width observed for the enriched methyl resonance is consistent with free rotation of the methyl group.

  DOI：

  10.1002/mrc.1270150210
• 作为产物：
  描述：

  2-[(2-甲基丙烷-2-基)氧基羰基氨基]-6-(苯基甲氧羰基氨基)己酸 (4-硝基苯基)酯 在 palladium on activated charcoal N-乙基吗啉 、 吡啶 、 盐酸 、 氨 、 氢气 作用下， 以 甲酸 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 N-α-acetyllysine amide
  参考文献：
  名称：

  [激素-受体相互作用。借助于对碱不稳定的保护基的合成α-促黑素及其信息序列（作者的翻译）]。

  摘要：

  Hormone‐Receptor Interactions. Synthesses of α‐Melanotropin and of Informational Sequences thereof with the Aid of Alcali‐Labile Protecting Groups.The aim of this investigation was to prepare α‐melanotropin and partial sequences thereof for biological investigations in as pure a state as possible. Classical synthesis in solution was chosen as the general approach, because it allows for extensive purification and identification of all intermediates, thus warranting the chemical identity of the products (in contrast to the solidphase methods). The scheme of protection was as follows: for the Nα‐amino groups mostly t‐butoxycarbonyl (BOC‐), sometimes benzyloxycarbonyl (Z‐), for the Nϵ‐amino group of lysine‐(11) 2‐(methylsulfonyl)‐ethoxycarbonyl (MSOC‐), and for the carboxylic acid group of C‐terminal glycine‐(10) 2‐(4‐tolyl‐sulfonyl)‐ethoxy (‐OTSE). This provides for facile and mild selective deprotection of either the α‐amino groups by acidolysis or of the ϵ‐amino group (α‐carboxyl group) by β‐elimination in alcali. A slight molar excess of 0.12N HCl in HCOOH proved to be the method of choice for removing BOC‐; MSOC‐ is stable in acid (even for 30 min in liquid HF) and easily removed in a few minutes by 0.05‐‐0.1N Ba(OH)2; ‐OTSE is removed similarly. Condensation of amino‐acid and peptide derivatives (formation of the peptide link) was performed using active esters (‐ONP; ‐OSU), dicyclohexyl‐carbodiimide (DCCI) with or without 1‐hydroxy‐benzotriazole (HOBT), or carboxylic acid azides wherever histidine was the carboxylic component.More than 50 compounds are described. Those characterized by arabic numerals served to prove that α‐MSH contains two message sequences that are able to trigger melanocyte response: one in the central region ‐His‐Phe‐Arg‐Trp‐, the other in the C‐terminal portion ‐Gly‐Lys‐Pro‐Val · NH2 of the molecule [3].

  DOI：

  10.1002/hlca.19750580724

文献信息

• Photochemical Nucleophile Mapping: Identification of Tyr311 Within the Catalytic Domain of Rabbit Muscle Glyceraldehyde‐3‐phosphate Dehydrogenase^†
  作者：Yasumaru Hatanaka、Masaki Kaneda、Takenori Tomohiro

  DOI：10.1562/2006-02-28-ra-824

  日期：2007.1

  Photochemical mapping of nucleophiles in close proximity to the active site Cys149 of rabbit glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) was demonstrated based on the nucleophilic aromatic photosubstitution reaction using two regioisomers of alkoxy‐fluoro‐nitro‐substituted benzenes. Two photophores were covalently attached to the active site SH group of GAPDH and the protein was subjected to photolysis then to the cyanogen bromide cleavage reaction. The advantage of this method is the capability to chase labeled products by monitoring absorption at 380 nm because of the chromogenic property of photophore. HPLC separation identified a large labeled peptide fragment that was further digested by V8 protease for Edman sequence analysis. From the recent X‐ray crystallography of rabbit GAPDH, Tyr311, His176, Ser238 and Lys183 are closely located to catalytic Cys149. Among these nucleophiles, Tyr311 was preferentially labeled with 2‐fluoro‐4‐nitrophenoxy photophore and no label was identified with the isomeric 4‐fluoro‐2‐nitrophenoxy photophore. The result clearly reflects the distance between Cys149 and nucleophiles to distinguish the nearest Tyr311. As photophores show great reactivity even with water under neutral conditions, the distance between nucleophiles and photophores is important for photo‐induced nucleophilic aromatic substitution. The method will provide a useful technique to survey nucleophiles within the catalytic domain.

  摘要利用烷氧基-氟-硝基取代苯的两个区域异构体进行亲核芳香族光取代反应，证明了靠近兔甘油醛-3-磷酸脱氢酶（GAPDH）活性位点 Cys149 的亲核物的光化学图谱。两个光敏剂共价连接到 GAPDH 的活性位点 SH 基团上，然后对蛋白质进行光解，再进行溴化氰裂解反应。这种方法的优点是，由于光团具有发色性，可以通过监测 380 纳米波长的吸收来追寻标记产物。高效液相色谱分离确定了一个大的标记肽片段，该片段被 V8 蛋白酶进一步消化，用于 Edman 序列分析。根据最近对兔 GAPDH 的 X 射线晶体学研究，Tyr311、His176、Ser238 和 Lys183 与催化 Cys149 的位置非常接近。在这些亲核物中，Tyr311 优先被 2-氟-4-硝基苯氧基光致发光体标记，而同分异构的 4-氟-2-硝基苯氧基光致发光体则没有标记。这一结果清楚地反映了 Cys149 与亲核物之间的距离，以区分最近的 Tyr311。由于在中性条件下，亲光体甚至与水也有很大的反应活性，因此亲核物与亲光体之间的距离对于光诱导的亲核芳香取代非常重要。该方法将为研究催化域内的亲核物提供有用的技术。
• .alpha.-Melanotropin: the minimal active sequence in the frog skin bioassay
  作者：Victor J. Hruby、Brian C. Wilkes、Mac E. Hadley、Fahad Al-Obeidi、Tomi K. Sawyer、Douglas J. Staples、Ann E. DeVaux、Orin Dym、Ana Maria de L. Castrucci

  DOI：10.1021/jm00394a033

  日期：1987.11

  yielded the peptide, Ac-alpha-MSH4-12-NH2 with a 360-fold increase in potency relative to Ac-alpha-MSH4-10-NH2. This peptide was only about 6-fold less potent than alpha-MSH. A series of Nle-4-substituted analogues also were prepared. Ac-[Nle4]-alpha-MSH4-10-NH2 was about 4 times more potent than Ac-alpha-MSH4-10-NH2. Ac-[Nle4]-alpha-MSH4-11-NH2 also was about 4 times more potent than Ac-alpha-MSH4-10-NH2

  在青蛙（Rpi pipiens）皮肤生物测定中确定了α-MSH（α-促黑素，α-黑素细胞刺激激素）的生物学活性所需的最小序列。引发可测量的生物学活性所需的序列是中央四肽序列Ac-His-Phe-Arg-Trp-NH2（Ac-alpha-MSH6-9-NH2），其效力比天然三肽低约6个数量级。 。此序列的较小片段（Ac-His-Phe-NH2，Ac-Phe-Arg-NH2，Ac-His-Phe-Arg-NH2）在高达10（-4）M的浓度下均不具有黑色素活性。无法证明四肽Ac-Phe-Arg-Trp-Gly-NH2（Ac-alpha-MSH7-10-NH2）和包括Ac-Lys-Pro-Val-NH2（ Ac-alpha-MSH11-13-NH2）。我们准备了一系列α-MSH的片段类似物，以试图确定每个氨基酸对天然激素的生物学活性的贡献。通过在C末端添加甘氨酸，可将Ac-alpha-MSH6-9
• Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine‐Selective Protein Modification and Charge Modulation
  作者：Maria J. Matos、Claudio D. Navo、Tuuli Hakala、Xhenti Ferhati、Ana Guerreiro、David Hartmann、Barbara Bernardim、Kadi L. Saar、Ismael Compañón、Francisco Corzana、Tuomas P. J. Knowles、Gonzalo Jiménez‐Osés、Gonçalo J. L. Bernardes

  DOI：10.1002/anie.201901405

  日期：2019.5.13

  introduces a +1 charge to the overall net charge of the protein, which enabled us to show that the electrophoretic mobility of the protein may be tuned through the simple attachment of a quaternized vinyl pyridinium reagent at the cysteine residues. We anticipate the generalized use of quaternized vinyl- and alkynyl-pyridine reagents not only for bioconjugation, but also as warheads for covalent inhibition

  已显示季铵化的乙烯基和炔基吡啶试剂与几种半胱氨酸标记的蛋白以接近化学计量的量以超快和选择性的方式反应。我们已经证明，该方法可以有效地创建均一的抗体与药物的结合物，其药物与抗体的精确比例为2，该比例在人血浆中稳定并且保留了其对Her2 +细胞的特异性。最后，发达的战斗部将蛋白质的总净电荷引入+1电荷，这使我们能够证明蛋白质的电泳迁移率可以通过在半胱氨酸残基上简单连接季铵化乙烯基吡啶鎓试剂来调节。我们预计，季铵化的乙烯基和炔基吡啶试剂不仅可用于生物缀合，
• [EN] MEXILETINE PRODRUGS<br/>[FR] PROMÉDICAMENTS DE MÉXILÉTINE
  申请人：SHIRE LLC

  公开号：WO2012085586A1

  公开（公告）日：2012-06-28

  The present invention concerns prodrugs of mexiletine (and mexiletine's active metabolite) pharmaceutical compositions containing such prodrugs. Methods for treating myotonic conditions, while reducing the inherent adverse G1 side effects associated with mexiletine, increasing the bioavailability of mexiletine, and improving the pharmacokinetic reproducibility of mexiletine with the aforementioned prodrugs are also provided.

  本发明涉及美西利汀（及美西利汀的活性代谢物）的前药，包含这些前药的药物组合物。还提供了用于治疗肌张力疾病的方法，同时减少与美西利汀相关的固有不良G1副作用，增加美西利汀的生物利用度，并通过上述前药改善美西利汀的药代动力学可重复性。
• Potent and Selective Inhibitors of Human Sirtuin 5
  作者：Diana Kalbas、Sandra Liebscher、Theresa Nowak、Marat Meleshin、Martin Pannek、Corinna Popp、Zayan Alhalabi、Frank Bordusa、Wolfgang Sippl、Clemens Steegborn、Mike Schutkowski

  DOI：10.1021/acs.jmedchem.7b01648

  日期：2018.3.22

  Sirtuins are protein deacylases that regulate metabolism and stress responses and are implicated in aging-related diseases. Modulators of the human sirtuins Sirt1–7 are sought as chemical tools and potential therapeutics, e.g., for cancer. Selective and potent inhibitors are available for Sirt2, but selective inhibitors for Sirt5 with Ki values in the low nanomolar range are lacking. We synthesized

  Sirtuins是调节代谢和应激反应的蛋白质脱酰基酶，与衰老相关的疾病有关。人们正在寻找人类sirtuins Sirt1-7的调节剂，作为化学工具和潜在疗法，例如用于癌症。选择性的和有效的抑制剂可用于Sirt2的，但对于Sirt5的选择性抑制剂与ķ我在低纳摩尔范围内的值所缺乏的。我们合成并筛选了可产生具有低纳摩尔K i的Sirt5抑制剂的3-芳基硫代琥珀酰化和3-苄基硫代琥珀酰化的肽衍生物。价值观。具有该支架的生物素化衍生物代表人Sirt5的亲和探针，该探针能够从复杂的生物样品（如细胞裂解物中）选择性地提取这种酶。Sirt5 /抑制剂复合物的晶体结构表明，该化合物以意想不到的方式与Sirt5的活性位点结合。