2-azidoethyl α-5-acetamido-9-(biphenylcarbonylamino)-3,5,9-trideoxy-D-glycero-2-nonulosonic acid-pyranosyl-(2->3)-β-D-galactopyranosyl-(1->3)-2-acetamido-2-deoxy-glucopyranoside | 1019642-47-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-azidoethyl α-5-acetamido-9-(biphenylcarbonylamino)-3,5,9-trideoxy-D-glycero-2-nonulosonic acid-pyranosyl-(2->3)-β-D-galactopyranosyl-(1->3)-2-acetamido-2-deoxy-glucopyranoside
• 英文别名: (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4S,5R,6S)-6-[(2R,3S,4R,5R,6R)-5-acetamido-6-(2-azidoethoxy)-4-hydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methoxy]-6-[(1R,2R)-1,2-dihydroxy-3-[(4-phenylbenzoyl)amino]propyl]-4-hydroxyoxane-2-carboxylic acid
• CAS: 1019642-47-7
• 化学式: C₄₀H₅₄N₆O₁₉
• 分子量: 922.898
• InChiKey: UTCPJMHBEGWJPH-LPKWDFCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  65
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  356
• 氢给体数：
  12
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  2-azidoethyl α-5-acetamido-9-(biphenylcarbonylamino)-3,5,9-trideoxy-D-glycero-2-nonulosonic acid-pyranosyl-(2->3)-β-D-galactopyranosyl-(1->3)-2-acetamido-2-deoxy-glucopyranoside 在 三甲基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 2-aminoethyl 5-acetamido-9-(4-biphenylcarbonylamino)-3,5,9-trideoxy-α-D-glycero-D-galacto-2-nonulopyranosylonate-(2-6)-O-β-D-galactopyranosyl-(1-4)-O-2-acetamido-2-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  CD22 Ligands on a Natural N-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells

  摘要：

  CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. Binding affinity is increased by up to 1500-fold compared to the monovalent ligand, while maintaining the selectivity for hCD22 over other Siglecs. Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs.

  DOI：

  10.1021/jacs.7b03208
• 作为产物：
  描述：

  5-acetamido-9-azido-3,5,9-trideoxy-D-glycero-D-galacto-2-nonulopyranosonic acid 在 CMP-sialic acid synthetase 、 α2−6-sialyltransferase hST6Gal-I 、 N,N-二异丙基乙胺 、 胞苷-5’-三磷酸 、 magnesium chloride 、 三甲基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 2-azidoethyl α-5-acetamido-9-(biphenylcarbonylamino)-3,5,9-trideoxy-D-glycero-2-nonulosonic acid-pyranosyl-(2->3)-β-D-galactopyranosyl-(1->3)-2-acetamido-2-deoxy-glucopyranoside
  参考文献：
  名称：

  CD22 Ligands on a Natural N-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells

  摘要：

  CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. Binding affinity is increased by up to 1500-fold compared to the monovalent ligand, while maintaining the selectivity for hCD22 over other Siglecs. Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs.

  DOI：

  10.1021/jacs.7b03208

文献信息

• On-Virus Construction of Polyvalent Glycan Ligands for Cell-Surface Receptors
  作者：Eiton Kaltgrad、Mary K. O'Reilly、Liang Liao、Shoufa Han、James C. Paulson、M. G. Finn

  DOI：10.1021/ja077801n

  日期：2008.4.1

  Glycans arrayed on the exterior of virus particles were used as substrates for glycosyltransferase reactions to build di- and trisaccharides from the virus surface. The resulting particles exhibited tight and specific associations with cognate receptors beads and cells, in one example defeating in cis cell-surface interactions in a manner characteristic of polyvalent binding. Combined with the ability of viruses to provide structurally well-defined attachment points, the methodology provides a convenient and powerful way to prepare complex carbohydrate ligands for clustered receptors.
• CD22 Ligands on a Natural <i>N</i>-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells
  作者：Wenjie Peng、James C. Paulson

  DOI：10.1021/jacs.7b03208

  日期：2017.9.13

  CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. Binding affinity is increased by up to 1500-fold compared to the monovalent ligand, while maintaining the selectivity for hCD22 over other Siglecs. Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs.