N^α-Fmoc-Ser(Ac3-β-D-GlcNAc)-OPfp | 160410-57-1

• 物质功能分类: 化学试剂 - 有机试剂 - 多环化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N^α-Fmoc-Ser(Ac3-β-D-GlcNAc)-OPfp
• 英文别名: (2,3,4,5,6-pentafluorophenyl) (2S)-3-[(2R,3R,4R,5S,6R)-3-acetamido-4,5-diacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoate
• CAS: 160410-57-1
• 化学式: C₃₈H₃₅F₅N₂O₁₃
• 分子量: 822.694
• InChiKey: LZLIKDJRORPCKN-WGLUAUJZSA-N

物化性质

• 沸点：
  888.1±65.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  58
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  191
• 氢给体数：
  2
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  FMOC-L-缬氨酸五氟苯酯 、 乙酸酐 、 N-芴甲氧羰基甘氨酸五氟苯酯 、 N^α-Fmoc-Ser(Ac3-β-D-GlcNAc)-OPfp 生成 Ac-Val-Ser(β-D-GlcNAc)-Gly-NH2
  参考文献：
  名称：

  Comparison of N-Dts and N-Aloc in the solid-phase syntheses of O-GlcNAc glycopeptide fragments of RNA-polymerase II and mammalian neurofilaments

  摘要：

  The application of the glycosylated building blocks N-alpha-Fmoc-Ser(Ac-3-beta-D-GlcNAc)-OPfp 5, N-alpha-Fmoc-Thr(Ac-3-beta-D-GlcNAc)-OPfp 6, N-alpha-Fmoc-Ser(Ac-3-beta-D-GlcNDts)-OPfp 7 and N-alpha-Fmoc-Thr(Ac-3-beta-D-GlcNDts)-OPfp 8 in the solid-phase synthesis-of O-GlcNAc glycopeptides from the C-terminal domain repeating unit of RNA-polymerase II and the NF-L chain of mammalian neurofilaments is described. The removal of the N-dithiasuccinoyl (N-Dts) amino-protecting group was achieved rapidly and quantitatively by thiolysis with 2-sulfanylethanol or dithiothreitol after the incorporation of the building blocks into the resin-bound peptide. The O-GlcNAc glycopeptides 9-11, 13 and 15-21 were synthesised in good yields by comparative studies employing any of the building blocks 5-8. The O-GlcNAc glycopeptides were fully characterised by 1D- and 2D-H-1 NMR spectroscopy and ES-MS.

  DOI：

  10.1039/p19950002165
• 作为产物：
  描述：

  Acetic acid (2R,3S,4R,5R)-3-acetoxy-2-acetoxymethyl-6-bromo-5-(3,5-dioxo-[1,2,4]dithiazolidin-4-yl)-tetrahydro-pyran-4-yl ester 在 3 A molecular sieve 、 silver trifluoromethanesulfonate 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 N^α-Fmoc-Ser(Ac3-β-D-GlcNAc)-OPfp
  参考文献：
  名称：

  从 N-二硫代琥珀酰保护衍生物合成 2-乙酰氨基-2-脱氧-β-d-吡喃葡萄糖O-糖肽1-3

  摘要：

  2-乙酰氨基-2-脱氧-β-d-吡喃葡萄糖 (β-d-GlcpNAc)，在与丝氨酸 (Ser) 和苏氨酸 (Thr) 残基侧链羟基的 O-糖苷键中，经常在细胞核和细胞质中发现蛋白质。固相糖肽合成的“活性酯”方法需要 Nα-(9-芴基甲氧羰基)氨基酸五氟苯基酯 (Nα-Fmoc-AA-OPfp's) 的直接糖基化。所需的 Ser(β-d-GlcpNAc) 和 Thr(β-d-GlcpNAc) 结构单元的合成带来了由相应糖基供体中的 2-氨基取代基引起的特殊问题。用 2-N-酰基基团激活供体提供了相对不活泼的恶唑啉中间体，而原本有希望的邻苯二甲酰基 (Phth) 基团需要在高温下长时间进行碱处理才能将其去除，并且经常遇到不完全脱保护。二硫代琥珀酰基 (Dts) 基团以与 Phth 基团相同的方式提供二价保护，但具有在温和条件下快速去除的优点...

  DOI：

  10.1021/ja953529i

文献信息

• Simple and Efficient Preparation of O- and S-GlcNAcylated Amino Acids through InBr₃-Catalyzed Synthesis of β-<i>N</i>-Acetylglycosides from Commercially Available Reagents
  作者：Cesar A. De Leon、Geoffrey Lang、Marcos I. Saavedra、Matthew R. Pratt

  DOI：10.1021/acs.orglett.8b02182

  日期：2018.8.17

  The facile synthesis of serine, threonine, and cysteine β-glycosides using commercially available peracetylated β-N-acetylglucosamine (β-Ac4GlcNAc) and catalytic amounts of indium bromide (InBr3) is described. This method involves only inexpensive reagents that require no further modification or special handling. The reagents are simply mixed, dissolved, and refluxed to afford the GlcNAcylated amino

  丝氨酸，苏氨酸和半胱氨酸使用市售全乙酰化β-β糖苷的简便合成Ñ乙酰氨基葡萄糖（β-AC 4的GlcNAc）和催化量的溴化铟（INBR的3）进行说明。该方法仅涉及廉价的试剂，无需进一步修改或特殊处理。只需将试剂混合，溶解并回流，即可获得高产率（70-80％）的GlcNAcylated氨基酸。这种操作简单的程序应有助于O-GlcNAcylation的研究，而无需合成碳水化合物化学方面的专业知识。
• Versatile solid-phase thiolytic reduction of azido and N-Dts groups in the synthesis of haemoglobin (67–76) O-glycopeptides and photoaffinity labelled analogues to study glycan T-cell specificity
  作者：Ernst Meinjohanns、Morten Meldal、Teis Jensen、Ole Werdelin、Luisa Galli-Stampino、Søren Mouritsen、Klaus Bock

  DOI：10.1039/a606725e

  日期：——

  A series of O-glycosylated peptides and photoaffinity labelled glycopeptide analogues of the mouse haemoglobin-derived decapeptide Hb (67–76), VITAFNEGLK, which binds well to the MHC class II Ek molecule and is non-immunogenic in CBA/J mice, was synthesized by multiple-column peptide synthesis employing the glycosylated building blocks 1–4 and 7–21. The non-immunogenic peptide VITAFNEGLK was converted into an immunogen by introducing different tumour-associated carbohydrate moieties [β-D-GlcNAc-O -Ser/Thr, α-D-GalNAc-O-Ser/Thr (TN-antigen) core 1 (T-antigen), core 2, core 3 and core 4] to the central position Asn-72 in the decapeptide. Previous studies suggest that T cells may be capable of recognizing epitopes which are partially defined by glycans and may be in direct contact with the T-cell receptor. In order to study the specificity of glycan interactions with the T-cell receptor a series of corresponding glycopeptides labelled with 2-azidobenzamide on the carbohydrate amino function was synthesized. The glycan structure was varied with respect to O-GlcNAc, T and TN-antigen moieties and anomeric configuration. Throughout, efficient reduction of the N-dithiasuccinyl- and azido-functionality-containing building blocks 1, 2, 7, 8, 11, 12, 13, 16, 18 and 20 could be achieved either (i) in solution by utilizing simultaneous in situ reduction with Zn in THF–HOAc–Ac2O or (ii) on solid-phase upon treatment with diisopropylethylamine and an excess of dithiothreitol or α-mercapto-N-methylacetamide. N-Acetylation of the resin-bound glycopeptides furnished the O-glycopeptides 24, 25 and 31–36. No further modification of the carbohydrate moiety on the solid phase was required when utilizing the N-acetylated building blocks 3, 4, 9, 10, 14, 15, 17, 19 and 21. In addition, comparative studies with solid-phase reduction were conducted for the syntheses of the O-linked glycopeptides 24, 25 and 31–36 by employing any of the building blocks 1–4 and 7–21. The photoaffinity labelled glycopeptides 39–45 were synthesized by employing building blocks 1, 2, 7, 8 and 11–13 by reduction of azido or N-Dts functionalities by thiolysis with dithiothreitol and subsequent coupling of the activated photoaffinity label 38 to the glycanamino group of the resin-bound glycopeptides. The synthesized mucin O-glycopeptides 24, 25 and 31–36 and the photoaffinity labelled analogues 39–45 were fully characterized by 1D and 2D 1H NMR spectroscopy and by electrospray mass spectrometry.

  利用糖基化结构单元 1â4 和 7â21 通过多柱肽合成法合成了一系列 O-糖基化肽和光亲和标记的小鼠血红蛋白衍生十肽 Hb（67â76）的糖肽类似物 VITAFNEGLK，它能很好地与 MHC II 类 Ek 分子结合，并且对 CBA/J 小鼠无免疫原性。通过在十肽的中心位置 Asn-72 引入不同的肿瘤相关碳水化合物分子 [δ-D-GlcNAc-O-Ser/Thr、δ-D-GalNAc-O-Ser/Thr（TN 抗原）核心 1（T 抗原）、核心 2、核心 3 和核心 4]，将非免疫原性肽 VITAFNEGLK 转化为免疫原。 以往的研究表明，T 细胞可能能够识别部分由聚糖定义的表位，并可能与 T 细胞受体直接接触。为了研究聚糖与 T 细胞受体相互作用的特异性，我们合成了一系列在碳水化合物氨基功能上用 2- 叠氮苯甲酰胺标记的相应聚糖肽。聚糖结构随 O-GlcNAc、T 和 TN 抗原分子以及异构体构型的不同而变化。自始至终，含 N-二硫代丁二酰基和叠氮官能团的结构单元 1、2、7、8、11、12、13、16、18 和 20 都可以通过以下两种方法实现高效还原：(i) 在溶液中用 Zn 在 THFâHOAcâAc2O 中同时原位还原；或 (ii) 在固相上用二异丙基乙胺和过量的二硫苏糖醇或δ-巯基-N-甲基乙酰胺处理。对树脂结合的糖肽进行 N-乙酰化，可得到 O-糖肽 24、25 和 31â36。在使用 N-乙酰化结构单元 3、4、9、10、14、15、17、19 和 21 时，不需要在固相上进一步修饰碳水化合物分子。此外，在合成 O-连接糖肽 24、25 和 31â36 时，还进行了固相还原比较研究，采用的是 1â4 和 7â21 中的任何一种构建模块。光亲和标记的糖肽 39â45 是通过使用构建模块 1、2、7、8 和 11â13 合成的，方法是用二硫苏糖醇进行硫醇分解还原叠氮或 N-Dts 官能，然后将活化的光亲和标记 38 与树脂结合的糖肽的甘氨酸基偶联。通过一维和二维 1H NMR 光谱以及电喷雾质谱法，对合成的粘蛋白 O 型糖肽 24、25 和 31â36 以及光亲和标记的类似物 39â45 进行了全面鉴定。
• Early detection of diabetes
  申请人：Hart Gerald W.

  公开号：US09250248B2

  公开（公告）日：2016-02-02

  The present invention is based on the discovery that hexosamine, and in particular the dynamic O-GlcNAcylation of proteins (modification of proteins by the sugar N-acetylglucosamine) both causes insulin-resistance (a hallmark of type II diabetes) and is responsible for glucose toxicity in the disease. Accordingly, the invention provides methods of diagnosing a subject as having or at risk of having pre-diabetes or diabetes. Also provided are methods of characterizing hyperglycemia in a subject, methods of identifying a protein as being associated with hyperglycemia, and kits for detecting pre-diabetes or diabetes.

  本发明基于发现：六胺糖，尤其是蛋白质的动态O-GlcNAcylation（通过糖N-乙酰葡萄糖胺修饰蛋白质）既会导致胰岛素抵抗（2型糖尿病的标志），也会导致疾病中的葡萄糖毒性。因此，本发明提供了诊断受试者患有或有患前糖尿病或糖尿病风险的方法。还提供了表征受试者高血糖的方法，鉴定与高血糖相关的蛋白质的方法以及用于检测患有或有患前糖尿病的试剂盒。
• Vargas-Berenguel, Antonio; Meldal, Morten; Paulsen, Hans, Journal of the Chemical Society. Perkin transactions I, 1994, # 18, p. 2615 - 2620
  作者：Vargas-Berenguel, Antonio、Meldal, Morten、Paulsen, Hans、Bock, Klaus

  DOI：——

  日期：——
• Efficient synthesis of O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-ser/thr building blocks for spps of o-glcnac glycopeptides
  作者：Ernst Meinjohanns、Morten Meldal、Klaus Bock

  DOI：10.1016/0040-4039(95)01941-a

  日期：1995.12

  Suitably protected building blocks for solid-phase synthesis of beta-O-GlcNAc glycopeptides. N-alpha-Fmor-Ser(Ac-3-beta-D-GlcNAc)-OPfp 10 and N-alpha-Fmoc-Thr(AL(3)-beta-D-GlcNAc)-OPfp 11 have been synthesized by stereoselective glycosylation of N-alpha-Fmoc-Ser-OPfE 6 and N-alpha-Fmoc-Thr-OPfp 7, respectively. with the 2-trichloroethoxycarbonylamino (Teoc) glycosyl donors 3 and 5, followed by in situ reduction of the Teoc-group and simultaneous N-acetylation using zinc dust in tetrahydrofuranlacetic anhydridelacetic acid (3:2:1).