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 | 936547-19-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 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
• 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-aminoethoxy)-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: 936547-19-2
• 化学式: C₄₀H₅₆N₄O₁₉
• 分子量: 896.9
• InChiKey: ZZARCXJXQRNJQY-LPKWDFCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.2
• 重原子数：
  63
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  368
• 氢给体数：
  13
• 氢受体数：
  20

反应信息

• 作为产物：
  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

文献信息

• Sialoside Analogue Arrays for Rapid Identification of High Affinity Siglec Ligands
  作者：Ola Blixt、Shoufa Han、Liang Liao、Ying Zeng、Julia Hoffmann、Satoshi Futakawa、James C. Paulson

  DOI：10.1021/ja801052g

  日期：2008.5.1

  The siglec family of sialic acid binding proteins participates in diverse I cell surface biology that includes regulation of immune cell signaling and the interaction of neuronal cells with glial cells. The weak intrinsic affinity of the natural sialoside ligands has hampered the development of synthetic ligand based probes needed to elucidate their roles in siglec function. In this report, we describe a glycan microarray comprising a library of 9-acyl-substituted sialic acids incorporated into sialosides containing the Neu5Aca2-3Gal and Neu5Aca2-6Gal linkages commonly recognized by the siglecs. The array is demonstrated to exhibit utility for detecting 9-acyl substituents that increase the affinity of siglecs for their ligands. Substituents that increase affinity are anticipated to be useful for the design of high affinity ligand based probes of siglec function.
• 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.