(2S,4S,5R,6R)-5-acetamido-2-[(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-6-(2-azidoethoxy)-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid | 152623-63-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,4S,5R,6R)-5-acetamido-2-[(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-6-(2-azidoethoxy)-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid
• CAS: 152623-63-7
• 化学式: C₂₅H₄₂N₄O₁₉
• 分子量: 702.624
• InChiKey: SEVRVASZKYTQFQ-KOKJUCRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  48
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  338
• 氢给体数：
  12
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  (2S,4S,5R,6R)-5-acetamido-2-[(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-6-(2-azidoethoxy)-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid 在 10% palladium on active carbon 、 GalNAcE 氢气 、 nicotinamide adenine dinucleotide 、 manganese(ll) chloride 作用下， 以 乙醇 、 alkaline aq. solution 、 水 为溶剂， 反应 25.0h， 生成
  参考文献：
  名称：

  Chemoenzymatic synthesis of 2-azidoethyl-ganglio-oligosaccharides GD3, GT3, GM2, GD2, GT2, GM1, and GD1a

  摘要：

  We have synthesized several ganglio-oligosaccharide structures using glycosyltransferases from Campylobacter jejuni. The enzymes, alpha-(2 -> 3/8)-sialyltransferase (Cst-II), beta-(1 -> 4)-N-acetylgalactosaminyltransferase (CgtA), and beta-(1 -> 3)-galactosyltransferase (CgtB), were produced in large-scale fermentation from Escherichia coli and further characterized based on their acceptor specificities. 2-Azidoethyl-glycosides corresponding to the oligosaccharides of GD3 (alpha-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> 3)-beta-(D)-Galp-(1 -> 4) -beta-(D)-Glcp-), GT3 (alpha-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> 3)-beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-), GM2 (beta-(D)-GalpNAc-(1 -> 4)-[alpha-(D)-Neup5Ac-(2 -> 3)]-beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-), GD2 (beta-(D)-GalpNAc-(1 -> 4)-[alpha-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> 3)]-beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-), GT2 (beta-(D)-GalpNAc-(1 -> 4)-[(alpha-(D)-Neup5Ac-(2 -> 8)]-beta-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> -> 3)beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-), and GM1 (beta-(D)-Galp-(1 -> 3)-beta-(D)-GalpNAc-(1 -> 4)-[alpha-(D)-Neup5Ac-(2 -> 3)]-beta-(D)-Galp(1 -> 4)-beta-(D)-Glcp-) were synthesized in high yields (gram-scale). In addition, a mammalian a-(2 3)-sialyltransferase (ST3Gal 1) was used to sialylate GM1 and generate GD1a (alpha-(D)-Neup5Ac-(2 -> 3)-beta-(D)-Galp-(1 -> 3)-beta-(D)-GalpNAc-(1 -> 4)-[alpha-(D)-Neup5Ac-(2 -> 3)]-beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-) oligosaccharide. We also cloned and expressed a rat UDP-N-acetylglucosamine-4 '-epimerase (GaINAcE) in E. coli AD202 cells for cost saving in situ conversion of less expensive UDP-GIcNAc to UDP-GaINAc. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2005.06.008
• 作为产物：
  描述：

  1',2',3',6',2,3,4,6-octa-O-acetyl-β-D-lactose 在 甲醇 、 sodium methylate 、 碳酸氢铵 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 magnesium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.17h， 生成 (2S,4S,5R,6R)-5-acetamido-2-[(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-6-(2-azidoethoxy)-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid
  参考文献：
  名称：

  DNP修饰的基于GM3的抗癌疫苗的合成及其对癌症免疫疗法的免疫活性评估

  摘要：

  肿瘤相关的碳水化合物抗原（TACA）是疫苗开发的有吸引力的目标。在此背景下，我们描述了将人工TACA和糖工程结合起来用于癌症疫苗开发的策略。化学合成2,4-二苯苯基（DNP）修饰的GM3中间体，并将其与匙孔血蓝蛋白（KLH）偶联，然后测试所得生物偶联物作为候选疫苗的潜力。小鼠免疫学研究表明，DNP修饰的GM3（GM3-NHDNP）类似物通过募集抗DNP抗体来促进疫苗构建体向抗原加工细胞（APC）的靶向递送，引起强烈而快速的免疫反应。此外，内源性产生的抗DNP抗体，以及引发的针对GM3-NHDNP的抗体，

  DOI：

  10.1016/j.cclet.2021.04.034

文献信息

• Phage-Display Selection of a Human Single-Chain Fv Antibody Highly Specific for Melanoma and Breast Cancer Cells Using a Chemoenzymatically Synthesized G_M3−Carbohydrate Antigen
  作者：Kyung Joo Lee、Shenlan Mao、Chengzao Sun、Changshou Gao、Ola Blixt、Sandra Arrues、Louis G. Hom、Gunnar F. Kaufmann、Timothy Z. Hoffman、Avery R. Coyle、James Paulson、Brunhilde Felding-Habermann、Kim D. Janda

  DOI：10.1021/ja020737j

  日期：2002.10.1

  tumor cell lines and showed no measurable reactivity against the HDFa cells. Hence, we have demonstrated that a synthetic G(M3) panning reagent can be used to isolate a fully human scFv that is highly specific for native G(M3) on the surface of tumor cells. The result is a significant step toward effective immunotherapies for the treatment of cancer.

  细胞表面鞘糖脂 G(M3) 的过度表达与许多不同的癌症有关，包括皮肤癌、结肠癌、乳腺癌和肺癌。针对 G(M3) 表位的抗体在这些癌症的治疗中具有作为治疗剂的潜在应用。我们描述了两种 G(M3) 衍生试剂的化学酶法合成及其在噬菌体展示的人类单链 Fv (scFv) 抗体库的淘选中的用途，该文库来自癌症患者的血液。选择三个 scFv 噬菌体克隆 GM3A6、GM3A8 和 GM3A15 进行重组表达，并使用 BIAcore 和流式细胞术进行表征。使用纯化的可溶性 scFvs 的 BIAcore 测量产生解离常数 (K(d))，范围从 4.2 x 10(-7) 到 2.1 x 10(-5) M。流式细胞术用于评估每个 scFv 区分正常人细胞（人真皮成纤维细胞，HDFa）、黑色素瘤细胞（HMV-1、M21 和 C-8161）和乳腺癌细胞（BCM-1、BCM）的能力-2 和 BMS）。GM3A6
• Chemoenzymatic synthesis of 2-azidoethyl-ganglio-oligosaccharides GD3, GT3, GM2, GD2, GT2, GM1, and GD1a
  作者：Ola Blixt、Daniela Vasiliu、Kirk Allin、Nathan Jacobsen、Dawn Warnock、Nahid Razi、James C. Paulson、Stéphane Bernatchez、Michel Gilbert、Warren Wakarchuk

  DOI：10.1016/j.carres.2005.06.008

  日期：2005.9

  We have synthesized several ganglio-oligosaccharide structures using glycosyltransferases from Campylobacter jejuni. The enzymes, alpha-(2 -> 3/8)-sialyltransferase (Cst-II), beta-(1 -> 4)-N-acetylgalactosaminyltransferase (CgtA), and beta-(1 -> 3)-galactosyltransferase (CgtB), were produced in large-scale fermentation from Escherichia coli and further characterized based on their acceptor specificities. 2-Azidoethyl-glycosides corresponding to the oligosaccharides of GD3 (alpha-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> 3)-beta-(D)-Galp-(1 -> 4) -beta-(D)-Glcp-), GT3 (alpha-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> 3)-beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-), GM2 (beta-(D)-GalpNAc-(1 -> 4)-[alpha-(D)-Neup5Ac-(2 -> 3)]-beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-), GD2 (beta-(D)-GalpNAc-(1 -> 4)-[alpha-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> 3)]-beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-), GT2 (beta-(D)-GalpNAc-(1 -> 4)-[(alpha-(D)-Neup5Ac-(2 -> 8)]-beta-(D)-Neup5Ac-(2 -> 8)-alpha-(D)-Neup5Ac-(2 -> -> 3)beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-), and GM1 (beta-(D)-Galp-(1 -> 3)-beta-(D)-GalpNAc-(1 -> 4)-[alpha-(D)-Neup5Ac-(2 -> 3)]-beta-(D)-Galp(1 -> 4)-beta-(D)-Glcp-) were synthesized in high yields (gram-scale). In addition, a mammalian a-(2 3)-sialyltransferase (ST3Gal 1) was used to sialylate GM1 and generate GD1a (alpha-(D)-Neup5Ac-(2 -> 3)-beta-(D)-Galp-(1 -> 3)-beta-(D)-GalpNAc-(1 -> 4)-[alpha-(D)-Neup5Ac-(2 -> 3)]-beta-(D)-Galp-(1 -> 4)-beta-(D)-Glcp-) oligosaccharide. We also cloned and expressed a rat UDP-N-acetylglucosamine-4 '-epimerase (GaINAcE) in E. coli AD202 cells for cost saving in situ conversion of less expensive UDP-GIcNAc to UDP-GaINAc. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis of DNP-modified GM3-based anticancer vaccine and evaluation of its immunological activities for cancer immunotherapy
  作者：Han Lin、Haofei Hong、Lipeng Feng、Jie Shi、Zhifang Zhou、Zhimeng Wu

  DOI：10.1016/j.cclet.2021.04.034

  日期：2021.12

  revealed that the DNP-modified GM3 (GM3-NHDNP) analog elicited strong and rapid immune responses by recruiting anti-DNP antibodies to facilitate the targeted delivery of the vaccine construct to antigen processing cells (APCs). Moreover, the endogenously produced anti-DNP antibodies, together with the elicited antibodies against GM3-NHDNP, may synergistically promote tumor binding and cancer cell death

  肿瘤相关的碳水化合物抗原（TACA）是疫苗开发的有吸引力的目标。在此背景下，我们描述了将人工TACA和糖工程结合起来用于癌症疫苗开发的策略。化学合成2,4-二苯苯基（DNP）修饰的GM3中间体，并将其与匙孔血蓝蛋白（KLH）偶联，然后测试所得生物偶联物作为候选疫苗的潜力。小鼠免疫学研究表明，DNP修饰的GM3（GM3-NHDNP）类似物通过募集抗DNP抗体来促进疫苗构建体向抗原加工细胞（APC）的靶向递送，引起强烈而快速的免疫反应。此外，内源性产生的抗DNP抗体，以及引发的针对GM3-NHDNP的抗体，