L-赖氨酸-¹³C₆，¹⁵N₂盐酸盐 | 1200447-00-2

• 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
• 中文名称: L-赖氨酸-¹³C₆，¹⁵N₂盐酸盐
• 英文名称: [13C,15N]-L-lysine monohydrochloride
• 英文别名: L-Lysine-13C6,15N2 hydrochloride；(2S)-2,6-bis(15N)(azanyl)(1,2,3,4,5,6-13C6)hexanoic acid;hydrochloride
• CAS: 1200447-00-2
• 化学式: C₆H₁₄N₂O₂*ClH
• 分子量: 190.571
• InChiKey: BVHLGVCQOALMSV-GSMNGUNQSA-N

物化性质

• 熔点：
  263-264 °C (dec. )(lit.)
• 溶解度：
  酸水溶液（微溶，超声处理），水（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.05
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  89.3
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• WGK Germany：
  3
• 储存条件：
  2-8°C，储存时应使用惰性气体。

制备方法与用途

L-赖氨酸-13C₆,¹⁵N₂盐酸盐是一种标记了¹³C和¹⁵N的L-赖氨酸盐酸盐。作为一种人体必需氨基酸，L-赖氨酸盐酸盐具有多种益处，包括治疗疱疹、增加钙吸收、减少糖尿病相关疾病以及改善肠道健康。

反应信息

• 作为反应物：
  描述：

  L-赖氨酸-¹³C₆，¹⁵N₂盐酸盐 在 盐酸 、 水 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 Nα-benzyloxycarbonyl-L-(13C6,15N2)lysine
  参考文献：
  名称：

  Synthesis of a stable-isotope-labeled biotinylated pentasaccharide conjugate (EP217609), a dual-effect anticoagulant drug

  摘要：

  EP217609 是一种可中和的双效抗凝剂，目前正在心脏手术心肺旁路中进行临床研究。我们合成了稳定同位素标记的 EP217609，作为支持生物测定的质谱内标。EP217609 由三个结构单元经六个步骤合成，总收率为 42%，化学纯度大于 99%。因此，首先在由[13C,15N]-l-赖氨酸 2 分三步制备的 N 保护标记生物素-赖氨酸 4 和五糖-间隔胺 6 之间进行偶联。去除 8 上的 Cbz 保护基团，然后与活化的肽模拟构筑基块 10 相耦合，就得到了 EP217609 的直接前体，它可以在 1,2,4-噁二唑-5(2H)-酮催化氢解成脒后得到。

  DOI：

  10.1002/jlcr.1900

文献信息

• [EN] METHODS FOR SELECTIVELY MODIFYING AMINO ACIDS AND PRODUCTS MADE THEREBY<br/>[FR] PROCÉDÉS DE MODIFICATION SÉLECTIVE D'ACIDES AMINÉS ET PRODUITS FABRIQUÉS PAR CEUX-CI
  申请人：UNIV CALIFORNIA

  公开号：WO2021007127A1

  公开（公告）日：2021-01-14

  Disclosed herein are methods for the selective substitution of a hydrogen bonded to a carbon atom (e.g., a hydrogen of an aliphatic methylene group) of a compound, which comprise contacting the compound with a substituent in the presence of a BesD halogenase.

  本文披露了一种选择性替代化合物中与碳原子结合的氢（例如，脂肪族亚甲基基团的氢）的方法，包括在BesD卤素酶存在的情况下将化合物与取代基接触。
• Interrogating Substrate Selectivity and Composition of Endogenous Histone Deacetylase Complexes with Chemical Probes
  作者：Alexander Dose、Julia Sindlinger、Jan Bierlmeier、Ahmet Bakirbas、Klaus Schulze-Osthoff、Stephanie Einsele-Scholz、Markus Hartl、Frank Essmann、Iris Finkemeier、Dirk Schwarzer

  DOI：10.1002/anie.201508174

  日期：2016.1.18

  three sets of probes, which derived from different acetylation sites, and sequence context was found to have a strong impact on substrate recognition and composition of HDAC complexes. By investigating K382 acetylation of the tumor suppressor p53 as an example, we further demonstrate that the interaction profiles reflect the catalytic activities of respective HDACs. These results underline the utility

  组蛋白脱乙酰基酶（HDAC）通过去除调节性赖氨酸残基上的乙酰化标记来调节众多细胞蛋白的功能和活性。我们开发了基于肽的HDAC探针，其中包含各种长度的异羟肟酸氨基酸，以在已知的乙酰化位点的背景下取代修饰的赖氨酸残基。使用来自不同乙酰化位点的三组探针研究了所有人类HDAC的相互作用谱，发现序列背景对底物识别和HDAC复合物的组成有很大影响。通过研究肿瘤抑制因子p53的K382乙酰化，我们进一步证明了相互作用谱反映了各个HDAC的催化活性。
• Reversible DNA-Protein Cross-Linking at Epigenetic DNA Marks
  作者：Shaofei Ji、Hongzhao Shao、Qiyuan Han、Christopher L. Seiler、Natalia Y. Tretyakova

  DOI：10.1002/anie.201708286

  日期：2017.11.6

  The DNA epigenetic mark 5-formylcytosine (5fC) was found to form reversible conjugates with histone proteins in cells. The resulting DNA–protein cross-links involve a transient Schiff-base formation between Lys chains of proteins and the aldehyde group of 5fC. These reversible DNA–protein conjugates are likely to modify the chromatin structure and contribute to the epigenetic control of gene expression

  发现DNA表观遗传标记5-甲酰基胞嘧啶（5fC）与细胞中的组蛋白形成可逆结合物。由此产生的DNA-蛋白质交联涉及蛋白质的Lys链与5fC的醛基之间的短暂席夫碱形成。这些可逆的DNA-蛋白质结合物可能会修饰染色质结构，并有助于基因表达的表观遗传控制。
• Discovery of Itaconate-Mediated Lysine Acylation
  作者：Dongyang Liu、Weidi Xiao、Haoting Li、Yanling Zhang、Shouli Yuan、Chengxi Li、Suwei Dong、Chu Wang

  DOI：10.1021/jacs.3c02332

  日期：2023.6.14

  proteomics identified itaconylation sites in multiple functional proteins, including glycolytic enzymes and histones, some of which were confirmed by synthetic peptide standards. The discovery of lysine itaconylation opens up new areas for studying how itaconate participates in immunoregulation via protein post-translational modification.

  衣康酸盐是一种重要的抗菌和免疫调节代谢物，参与宿主-病原体相互作用。衣康酸盐的一个关键机制作用是通过迈克尔加成对半胱氨酸残基进行共价修饰，从而导致“衣康化”。然而，尚不清楚衣康酸盐是否具有其他调节机制。在这项工作中，我们通过开放搜索策略的混杂抗体富集和数据分析发现了一种新型的翻译后修饰，并进一步确认其为赖氨酸“衣康酰化”。我们表明衣康酰化及其前体代谢物衣康酰辅酶 A 在 RAW264.7 巨噬细胞中对脂多糖 (LPS) 刺激进行显着上调。定量蛋白质组学鉴定了多种功能蛋白中的衣康基化位点，包括糖酵解酶和组蛋白，其中一些已通过合成肽标准得到证实。赖氨酸衣康酰化的发现为研究衣康酸如何通过蛋白质翻译后修饰参与免疫调节开辟了新领域。
• New Biomarkers for Monitoring the Levels of Isothiocyanates in Humans
  作者：Anoop Kumar、Gabriele Sabbioni

  DOI：10.1021/tx900393t

  日期：2010.4.19

  Isothiocyanates (ITCs) found in cruciferous vegetables have demonstrated cancer preventive activity in animals, and increased dietary intake of ITCs has been shown to be associated with a reduced cancer risk in humans. ITCs exert their cancer chemopreventive action by multiple mechanisms, for example, by modulating the activities of phase 1 and phase II drug metabolism enzymes, by inhibiting the cell cycle and histone deacetylase, and by causing apoptotic cell death. In cells, protein adducts account for most of total cellular ITC uptake at 4 h after treatment. The time course of this protein binding correlates well with the inhibition of proliferation and the induction of apoptosis. Animal studies have shown that glutathione conjugates are the major products of ITCs. The major urinary excretion products of ITCs in human are N-acetyl cysteine conjugates. Urinary metabolites might provide the exposure history of the last 24 h, if the urine of the full next day is collected. However, this is not feasible in large epidemiological studies. Furthermore, the mercapturic acids of ITC are not stable. Therefore, stable biomarkers are needed that reflect a larger time span of the ITC exposure history. We developed a method to determine stable (not cysteine adducts) reaction products of ITCs with albumin and hemoglobin in humans and mice. We reacted albumin with the ITCs: benzyl isothiocyanate (BITC), phenylethyl isothiocyanate (PEITC), sulforaphane (SFN), and ally! isothiocyanate (AITC). After enzymatic digestion, we found one major product with lysine using LC-MS/MS. The identity of the adducts was confirmed by comparing the analyses with synthetic standards: N-6-[(benzylamino)carbonothioyl]lysine (BITC-Lys), N-6-[(2-phenylethypamino]carbonothioyl}lysine (PEITC-Lys), N-6-([3-(methylsulfinyl)propyl]amino}carbonothioyl)lysine (SFN-Lys), and N-6-[(allylamino]carbonothioyl]lysine (AITC-Lys). The adduct levels were quantified by isotope dilution mass spectrometry using the corresponding new ITC-[(C6N2)-C-13-N-15]lysines as internal standards. The applicability of the method was tested for biological samples obtained from different experiments. In humans consuming garden cress, watercress, and broccoli and/or in mice exposed chronically to N-acetyl-S-[(2-phenylethyl)amino]carbonothioyl}-L-cysteine, albumin and hemoglobin adducts were found. BITC-Lys, PEITC-Lys, and SFN-Lys released after enzymatic digestion of the proteins were quantified with LC-MS/MS. This new method will enable quantification of ITC adducts in blood proteins from large prospective studies about diet and cancer. Protein adducts are involved in the chemopreventive effects of ITCs. Therefore, blood protein adducts are a potential surrogate marker for the effects of ITCs at the cellular level. This new technique will improve the assessment of ITC exposure and the power of studies on the relationship between ITC intake and cancer.