2-azidoethyl (5-acetamido-9-(3-(4-methylphenyl)thiophene-2-carboxamido)-3,5,9-trideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2→3)-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranoside | 1397938-36-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-azidoethyl (5-acetamido-9-(3-(4-methylphenyl)thiophene-2-carboxamido)-3,5,9-trideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2→3)-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranoside
• 英文别名: (2S,4S,5R,6R)-5-acetamido-2-[(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-6-(2-azidoethoxy)-4-hydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-6-[(1R,2R)-1,2-dihydroxy-3-[[3-(4-methylphenyl)thiophene-2-carbonyl]amino]propyl]-4-hydroxyoxane-2-carboxylic acid
• CAS: 1397938-36-1
• 化学式: C₃₉H₅₄N₆O₁₉S
• 分子量: 942.953
• InChiKey: YRGDSHBIXPGTOU-CRBCASJVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  65
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  384
• 氢给体数：
  12
• 氢受体数：
  22

反应信息

• 作为产物：
  描述：

  2-azidoethyl (β-D-galactopyranosyl)-(1->4)-O-2-acetamido-2-deoxy-β-D-glucopyranoside 在 pasteurella multocida α2−3-sialyltransferase 1 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 2-azidoethyl (5-acetamido-9-(3-(4-methylphenyl)thiophene-2-carboxamido)-3,5,9-trideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2→3)-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  In Silico-Aided Design of a Glycan Ligand of Sialoadhesin for in Vivo Targeting of Macrophages

  摘要：

  Cell-specific delivery of therapeutic agents using ligand targeting is gaining interest because of its potential for increased efficacy and reduced side effects. The challenge is to develop a suitable ligand for a cell-surface receptor that is selectively expressed on the desired cell. Sialoadhesin (Sn, Siglec-1, CD169), a sialic acid-binding immunoglobulin-like lectin (Siglec) expressed on subsets of resident and inflammatory macrophages, is an attractive target for the development of a ligand-targeted delivery system. Here we report the development of a high-affinity and selective ligancl for Sn that is an analogue of the natural ligand and is capable of targeting liposomal nanoparticles to Sn-expressing cells in vivo. An efficient in silico screen of a library of similar to 8400 carboxylic acids was the key to identifying novel 9-N-acyl-substituted N-acetylneuramic acid (Neu5Ac) substituents as potential lead compounds. A small panel of targets were selected from the screen and synthesized to evaluate their affinities and selectivities. The most potent of these Sn ligands, (4H-thieno[3,2-c]chromene-2-carbamoyl)-Neu5Ac alpha 2-3Gal beta 1-4GlcNAc ((TCC)Neu5Ac), was conjugated to lipids for display on a liposomal nanoparticle for evaluation of targeted delivery to cells. The (TCC)Neu5Ac liposomes were found to target liposomes selectively to cells expressing either murine or human Sn in vitro, and when administered to mice, they exhibited in vivo targeting to Sn-positive macrophages.

  DOI：

  10.1021/ja307501e

文献信息

• In Silico-Aided Design of a Glycan Ligand of Sialoadhesin for in Vivo Targeting of Macrophages
  作者：Corwin M. Nycholat、Christoph Rademacher、Norihito Kawasaki、James C. Paulson

  DOI：10.1021/ja307501e

  日期：2012.9.26

  Cell-specific delivery of therapeutic agents using ligand targeting is gaining interest because of its potential for increased efficacy and reduced side effects. The challenge is to develop a suitable ligand for a cell-surface receptor that is selectively expressed on the desired cell. Sialoadhesin (Sn, Siglec-1, CD169), a sialic acid-binding immunoglobulin-like lectin (Siglec) expressed on subsets of resident and inflammatory macrophages, is an attractive target for the development of a ligand-targeted delivery system. Here we report the development of a high-affinity and selective ligancl for Sn that is an analogue of the natural ligand and is capable of targeting liposomal nanoparticles to Sn-expressing cells in vivo. An efficient in silico screen of a library of similar to 8400 carboxylic acids was the key to identifying novel 9-N-acyl-substituted N-acetylneuramic acid (Neu5Ac) substituents as potential lead compounds. A small panel of targets were selected from the screen and synthesized to evaluate their affinities and selectivities. The most potent of these Sn ligands, (4H-thieno[3,2-c]chromene-2-carbamoyl)-Neu5Ac alpha 2-3Gal beta 1-4GlcNAc ((TCC)Neu5Ac), was conjugated to lipids for display on a liposomal nanoparticle for evaluation of targeted delivery to cells. The (TCC)Neu5Ac liposomes were found to target liposomes selectively to cells expressing either murine or human Sn in vitro, and when administered to mice, they exhibited in vivo targeting to Sn-positive macrophages.