3-(2-aminoethylthio)propyl (β-D-galactopyranosyl)-(1-3)-2-acetamido-2-deoxy-α-D-galactopyranoside

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(2-aminoethylthio)propyl (β-D-galactopyranosyl)-(1-3)-2-acetamido-2-deoxy-α-D-galactopyranoside
• 英文别名: N-[(2S,3R,4R,5R,6R)-2-[3-(2-aminoethylsulfanyl)propoxy]-5-hydroxy-6-(hydroxymethyl)-4-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-3-yl]acetamide
• 化学式: C₁₉H₃₆N₂O₁₁S
• 分子量: 500.568
• InChiKey: DZAOLYAFNKNTJU-ZKTTVSFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  239
• 氢给体数：
  8
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  丙烯酰氯 、 3-(2-aminoethylthio)propyl (β-D-galactopyranosyl)-(1-3)-2-acetamido-2-deoxy-α-D-galactopyranoside 在 Resin-OH^- 作用下， 以 甲醇 为溶剂， 以100%的产率得到
  参考文献：
  名称：

  Direct targeted glycation of the free sulfhydryl group of cysteine residue (Cys-34) of BSA. Mapping of the glycation sites of the anti-tumor Thomsen-Friedenreich neoglycoconjugate vaccine prepared by Michael addition reaction

  摘要：

  我们在本手稿中介绍了汤姆森-弗里登莱希抗原-BSA 疫苗（TF 抗原：BSA）的确切糖化位点特征，该疫苗是利用亲电受体糖类抗原与 BSA 的亲核硫醇和 L-赖氨酸ε-氨基之间的迈克尔加成反应，并采用不同的连接条件制备而成的。在 TF 抗原与蛋白质的比例为 2:1 和 8:1 时，对制备的新甘糖共轭物进行基质激光解吸电离飞行时间质谱分析，可分别观察到每种新甘糖共轭物的质子化分子：[M + H]+ 在 m/z 67 599 和 70 905。通过测量这些分子量，我们可以准确地确认这两种合成疫苗的碳水化合物与蛋白质的比例。结果发现，TF 抗原与 BSA 的比例分别为 2:1 和 8:1，二者十分接近。通过胰蛋白酶消化和液相色谱-电喷雾离子化质谱法，我们确定了一系列释放的糖肽和肽片段。随后，我们利用低能碰撞解离串联质谱法进行了新测序，从而揭示了这些新糖结合疫苗的精确糖化位点。最后，我们为 TF 抗原与 BSA 比率为 2:1 的合成糖结合疫苗分别鉴定出了三个诊断性和特征性糖化肽，而为 TF 与 BSA 比率为 8:1 的合成糖结合疫苗鉴定出了一系列共 14 个糖化肽。这些新糖类共轭物占据位点的净增加是由于合成碳水化合物抗原与蛋白质载体的化学连接过程中产生了大量糖化形式。Copyright © 2014 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jms.3448
• 作为产物：
  描述：

  (2,3,4,6-tetra-O-benzoyl-α-D-galactopyranosyl)-(1-3)-2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-galactopyranoside 在 甲醇 、 sodium methylate 作用下， 以 水 为溶剂， 反应 6.5h， 生成 3-(2-aminoethylthio)propyl (β-D-galactopyranosyl)-(1-3)-2-acetamido-2-deoxy-α-D-galactopyranoside
  参考文献：
  名称：

  Synthesis of N,N‘-bis(Acrylamido)acetic Acid-Based T-Antigen Glycodendrimers and Their Mouse Monoclonal IgG Antibody Binding Properties

  摘要：

  Novel glycodendrimers based on N,N'-bis(acrylamido)acetic acid core with valencies between two and six were synthesized. The breast cancer-associated T-antigen carbohydrate marker, (beta -Gal-(1 -3)-alpha -GalNAc-OR), was then conjugated by (i) 1,4-conjugate addition of thiolated T-antigen to the N-acrylamido dendritic cores and by (ii) amide bond formation between an acid derivative of the T-antigen and the polyamino dendrimers. The protein-binding ability of these new glycodendrimers was fully demonstrated by turbidimetric analysis and by enzyme-linked immunosorbent assay (ELISA) using peanut lectin from Arachis hypogaea and a mouse monoclonal antibody (MAb) FAA-J11 (IgG3). When tested as inhibitors of binding between: MAb and a polymeric form of the T-antigen (T-antigen-co-polyacrylamide) used as a coating antigen, di(17), tetra- (20), hexa- (21.), and tetravalent (22) dendrimers showed IC50 values of 174, 19, 48, and 18 nM, respectively. Two tetramers showed 120- to similar to 128-fold increased inhibitory properties over the monovalent antigen 6 used as a standard (IC50 2.3 mM). Heterobifunctional glycodendrimer bearing a biotin probe was also prepared for cancer cell labeling.

  DOI：

  10.1021/ja002596w

文献信息

• Synthesis of <i>N</i>,<i>N</i>‘-bis(Acrylamido)acetic Acid-Based T-Antigen Glycodendrimers and Their Mouse Monoclonal IgG Antibody Binding Properties
  作者：René Roy、Myung-Gi Baek、Kate Rittenhouse-Olson

  DOI：10.1021/ja002596w

  日期：2001.3.1

  Novel glycodendrimers based on N,N'-bis(acrylamido)acetic acid core with valencies between two and six were synthesized. The breast cancer-associated T-antigen carbohydrate marker, (beta -Gal-(1 -3)-alpha -GalNAc-OR), was then conjugated by (i) 1,4-conjugate addition of thiolated T-antigen to the N-acrylamido dendritic cores and by (ii) amide bond formation between an acid derivative of the T-antigen and the polyamino dendrimers. The protein-binding ability of these new glycodendrimers was fully demonstrated by turbidimetric analysis and by enzyme-linked immunosorbent assay (ELISA) using peanut lectin from Arachis hypogaea and a mouse monoclonal antibody (MAb) FAA-J11 (IgG3). When tested as inhibitors of binding between: MAb and a polymeric form of the T-antigen (T-antigen-co-polyacrylamide) used as a coating antigen, di(17), tetra- (20), hexa- (21.), and tetravalent (22) dendrimers showed IC50 values of 174, 19, 48, and 18 nM, respectively. Two tetramers showed 120- to similar to 128-fold increased inhibitory properties over the monovalent antigen 6 used as a standard (IC50 2.3 mM). Heterobifunctional glycodendrimer bearing a biotin probe was also prepared for cancer cell labeling.
• Direct targeted glycation of the free sulfhydryl group of cysteine residue (Cys-34) of BSA. Mapping of the glycation sites of the anti-tumor Thomsen-Friedenreich neoglycoconjugate vaccine prepared by Michael addition reaction
  作者：Wael L. L. Demian、Naresh Kottari、Tze Chieh Shiao、Edward Randell、René Roy、Joseph H. Banoub

  DOI：10.1002/jms.3448

  日期：2014.12

  We present in this manuscript the characterization of the exact glycation sites of the Thomsen–Friedenreich antigen–BSA vaccine (TF antigen:BSA) prepared using a Michael addition reaction between the saccharide antigen as an electrophilic acceptor and the nucleophilic thiol and L-Lysine ε-amino groups of BSA using different ligation conditions. Matrix laser desorption ionization time-of-flight mass spectrometry of the neoglycoconjugates prepared with TF antigen:protein ratios of 2:1 and 8:1, allowed to observe, respectively, the protonated molecules for each neoglycoconjugates: [M + H]+ at m/z 67 599 and 70 905. The measurements of these molecular weights allowed us to confirm exactly the carbohydrate:protein ratios of these two synthetic vaccines. These were found to be closely formed by a TF antigen:BSA ratios of 2:1 and 8:1, respectively. Trypsin digestion and liquid chromatography coupled with electrospray ionization mass spectrometry allowed us to identify the series of released glycopeptide and peptide fragments. De novo sequencing affected by low-energy collision dissociation tandem mass spectrometry was then employed to unravel the precise glycation sites of these neoglycoconjugate vaccines. Finally, we identified, respectively, three diagnostic and characteristic glycated peptides for the synthetic glycoconjugate possessing a TF antigen:BSA ratio 2:1, whereas we have identified for the synthetic glycoconjugate having a TF:BSA ratio 8:1 a series of 14 glycated peptides. The net increase in the occupancy sites of these neoglycoconjugates was caused by the large number of glycoforms produced during the chemical ligation of the synthetic carbohydrate antigen onto the protein carrier. Copyright © 2014 John Wiley & Sons, Ltd.

  我们在本手稿中介绍了汤姆森-弗里登莱希抗原-BSA 疫苗（TF 抗原：BSA）的确切糖化位点特征，该疫苗是利用亲电受体糖类抗原与 BSA 的亲核硫醇和 L-赖氨酸ε-氨基之间的迈克尔加成反应，并采用不同的连接条件制备而成的。在 TF 抗原与蛋白质的比例为 2:1 和 8:1 时，对制备的新甘糖共轭物进行基质激光解吸电离飞行时间质谱分析，可分别观察到每种新甘糖共轭物的质子化分子：[M + H]+ 在 m/z 67 599 和 70 905。通过测量这些分子量，我们可以准确地确认这两种合成疫苗的碳水化合物与蛋白质的比例。结果发现，TF 抗原与 BSA 的比例分别为 2:1 和 8:1，二者十分接近。通过胰蛋白酶消化和液相色谱-电喷雾离子化质谱法，我们确定了一系列释放的糖肽和肽片段。随后，我们利用低能碰撞解离串联质谱法进行了新测序，从而揭示了这些新糖结合疫苗的精确糖化位点。最后，我们为 TF 抗原与 BSA 比率为 2:1 的合成糖结合疫苗分别鉴定出了三个诊断性和特征性糖化肽，而为 TF 与 BSA 比率为 8:1 的合成糖结合疫苗鉴定出了一系列共 14 个糖化肽。这些新糖类共轭物占据位点的净增加是由于合成碳水化合物抗原与蛋白质载体的化学连接过程中产生了大量糖化形式。Copyright © 2014 John Wiley & Sons, Ltd. All Rights Reserved.