炔基修饰甘露糖 | 935658-93-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 炔基修饰甘露糖
• 英文名称: 1,3,4,6-tetra-O-acetyl-N-4-pentynoylmannosamine
• 英文别名: peracetylated N-(4-pentynoyl)mannosamine；peracetylated N-(4-pentynoyl)-D-mannosamine；2-(N-4-pentynoylamino)-2-deoxy-1,3,4,6-tetra-O-acetyl-D-mannopyranoside；Ac₄ManNAl；1,3,4,6-tetra-O-acetyl-N-(4-pentynoyl)-D-mannosamine；ManNAcyne；2-[(1-Oxo-4-pentynyl)amino]-1-O,3-O,4-O,6-O-tetraacetyl-2-deoxy-D-mannopyranose；[(2R,3S,4R,5S)-3,4,6-triacetyloxy-5-(pent-4-ynoylamino)oxan-2-yl]methyl acetate
• CAS: 935658-93-8
• 化学式: C₁₉H₂₅NO₁₀
• 分子量: 427.408
• InChiKey: PODQGPKRSTUNAT-APCIHPPFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  144
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  炔基修饰甘露糖 、 5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[[2-[(3-azido-2-oxochromen-7-yl)-methylamino]acetyl]amino]ethoxy]ethoxy]ethyl]pentanamide 在 tris(triazolyl)amine 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 二甲基亚砜 为溶剂， 生成
  参考文献：
  名称：

  Development of trifunctional probes for glycoproteomic analysis

  摘要：

  一种新的三功能探针，通过可切割的链接器组装而成，有助于高效富集和检测带有炔基糖标记的生物分子。

  DOI：

  10.1039/c0cc00345j
• 作为产物：
  描述：

  炔丙基脲 在 吡啶 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 炔基修饰甘露糖
  参考文献：
  名称：

  Cellular Consequences of Copper Complexes Used To Catalyze Bioorthogonal Click Reactions

  摘要：

  Copper toxicity is a critical issue in the development of copper-based catalysts for copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions for applications in living systems. The effects and related toxicity of copper on mammalian Cells are dependent on the ligand environment. Copper complexes can be highly toxic, can induce changes in cellular metabolism; and can be. rapidly taken up by cells all of which can affect their ability to function as catalysts for CuAAC in living systems.. Herein, we have evaluated the effects Of a number of copper complexes that are typically Used, to catalyze CuAAC reactions on four human cell lines by measuring. mitochondrial activity based on the Metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to study toxicity, inductively coupled plasma mass spectrometry to study cellular uptake, and coherent anti Stokes Raman scattering (CARS) microscopy to study effects on lipid metabolism. We find that ligand:environment around copper influences all three parameters. Interestingly,for the Cu(II)-bis-L-histidine complex (Cu(his)(2)), cellular uptake and metabolic changes are observed with no toxicity after 72 h at micromolar concentrations. Furthermore, we show that under conditions where other copper complexes kill human hepatoma cells, Cu(I)-L-histidine is an effective catalyst for CuAAC labeling of live cells following metabolic incorporation of an alkyne-labeled sugar (Ac(4)ManNAl) into glycosylated proteins expressed on the cell surface. This result suggests that Cu(his)2 or derivatives thereof have potential for in vivo applications where toxicity as well as catalytic activity are critical factors for successful bioconjugation reactions.

  DOI：

  10.1021/ja2083027

文献信息

• Alkynyl sugar analogs for labeling and visualization of glycoconjugates in cells
  申请人：Sawa Masaaki

  公开号：US09816981B2

  公开（公告）日：2017-11-14

  Methods for metabolic oligosaccharide engineering that incorporates derivatized alkyne-bearing sugar analogs as “tags” into cellular glycoconjugates are disclosed. Alkynyl derivatized Fuc and alkynyl derivatized ManNAc sugars are incorporated into cellular glycoconjugates. Chemical probes comprising an azide group and a visual or fluorogenic probe and used to label alkyne-derivatized sugar-tagged glycoconjugates are disclosed. Chemical probes bind covalently to the alkynyl group by Cu(I)-catalyzed [3+2] azide-alkyne cycloaddition and are visualized at the cell surface, intracellularly, or in a cellular extract. The labeled glycoconjugate is capable of detection by flow cytometry, SDS-PAGE, Western blot, ELISA, confocal microscopy, and mass spectrometry.

  揭示了一种代表性的代谢性寡糖工程方法，该方法将衍生的烷基糖类类似物作为“标签”并加入到细胞糖联合物中。烷基化的Fuc和烷基化的ManNAc糖被纳入到细胞糖联合物中。揭示了一种化学探针，包括一个偶氮基团和一个可视或荧光探针，并用于标记烷基化糖标记的糖联合物。化学探针通过Cu（I）催化的[3+2]偶氮-烷基环加成与烷基基团共价结合，并在细胞表面、细胞内或细胞提取物中可视化。标记的糖联合物能够通过流式细胞术、SDS-PAGE、Western blot、ELISA、共聚焦显微镜和质谱检测进行检测。
• Metabolic Glycoengineering in hMSC-TERT as a Model for Skeletal Precursors by Using Modified Azide/Alkyne Monosaccharides
  作者：Stephan Altmann、Jürgen Mut、Natalia Wolf、Jutta Meißner-Weigl、Maximilian Rudert、Franz Jakob、Marcus Gutmann、Tessa Lühmann、Jürgen Seibel、Regina Ebert

  DOI：10.3390/ijms22062820

  日期：——

  Metabolic glycoengineering enables a directed modification of cell surfaces by introducing target molecules to surface proteins displaying new features. Biochemical pathways involving glycans differ in dependence on the cell type; therefore, this technique should be tailored for the best results. We characterized metabolic glycoengineering in telomerase-immortalized human mesenchymal stromal cells (hMSC-TERT) as a model for primary hMSC, to investigate its applicability in TERT-modified cell lines. The metabolic incorporation of N-azidoacetylmannosamine (Ac4ManNAz) and N-alkyneacetylmannosamine (Ac4ManNAl) into the glycocalyx as a first step in the glycoengineering process revealed no adverse effects on cell viability or gene expression, and the in vitro multipotency (osteogenic and adipogenic differentiation potential) was maintained under these adapted culture conditions. In the second step, glycoengineered cells were modified with fluorescent dyes using Cu-mediated click chemistry. In these analyses, the two mannose derivatives showed superior incorporation efficiencies compared to glucose and galactose isomers. In time-dependent experiments, the incorporation of Ac4ManNAz was detectable for up to six days while Ac4ManNAl-derived metabolites were absent after two days. Taken together, these findings demonstrate the successful metabolic glycoengineering of immortalized hMSC resulting in transient cell surface modifications, and thus present a useful model to address different scientific questions regarding glycosylation processes in skeletal precursors.

  代谢性糖基工程能够通过向表现新特征的表面蛋白质引入目标分子，实现对细胞表面的定向修饰。涉及糖基的生化途径因细胞类型而异，因此该技术应根据实际情况进行调整以获得最佳效果。我们以端粒酶不老化人骨髓基质干细胞（hMSC-TERT）作为原代hMSC的模型，对代谢性糖基工程进行了表征，以研究其在TERT修饰的细胞系中的适用性。将N-azidoacetylmannosamine（Ac4ManNAz）和N-alkyneacetylmannosamine（Ac4ManNAl）代谢性地引入糖环作为糖基工程过程的第一步，结果显示对细胞存活率或基因表达没有不良影响，并且在这些适应性培养条件下，细胞的体外多能性（成骨和成脂分化潜能）得以维持。在第二步中，通过Cu介导的点击化学反应，将荧光染料修饰到糖基工程细胞上。在这些分析中，与葡萄糖和半乳糖异构体相比，这两种甘露糖衍生物显示出更高的糖环引入效率。在时间依赖性实验中，Ac4ManNAz的引入可检测到长达六天，而Ac4ManNAl衍生物在两天后消失。综上所述，这些发现证明了不老化hMSC的成功代谢性糖基工程，导致短暂的细胞表面修饰，因此提供了一个有用的模型，可用于解决关于骨骼前体细胞糖基化过程的不同科学问题。