1-[N'-2-acetamido-2-deoxy-β-D-galactopyranosyl-(1->4-2-acetamido-2-deoxy-β-D-glucopyranosyl)-thioureido]-10-[N'-(2-acetamido-2-deoxy-β-D-glucopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-galactopyranosyl)-thioureido]-decane | 1319018-61-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[N'-2-acetamido-2-deoxy-β-D-galactopyranosyl-(1->4-2-acetamido-2-deoxy-β-D-glucopyranosyl)-thioureido]-10-[N'-(2-acetamido-2-deoxy-β-D-glucopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-galactopyranosyl)-thioureido]-decane
• 英文别名: N-[(2R,3R,4R,5S,6R)-2-[10-[[(2R,3R,4R,5S,6R)-3-acetamido-5-[(2S,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]carbamothioylamino]decylcarbamothioylamino]-5-[(2S,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide
• CAS: 1319018-61-5
• 化学式: C₄₄H₇₈N₈O₂₀S₂
• 分子量: 1103.28
• InChiKey: KXDZJVQZEXQMFZ-YGZAUGSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.3
• 重原子数：
  74
• 可旋转键数：
  25
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  486
• 氢给体数：
  18
• 氢受体数：
  22

反应信息

• 作为产物：
  描述：

  2-乙酰氨基-2-脱氧-3,4,6-O-三乙酰基-beta-D-吡喃葡萄糖异硫氰酸酯 在 sodium methylate 、 N,N-二异丙基乙胺 、 manganese(ll) chloride 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 72.0h， 生成 1-[N'-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-thioureido]-10-[N'-(2-acetamido-2-deoxy-β-D-glucopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-galactopyranosyl)-thioureido]-decane 、 1-[N'-2-acetamido-2-deoxy-β-D-galactopyranosyl-(1->4-2-acetamido-2-deoxy-β-D-glucopyranosyl)-thioureido]-10-[N'-(2-acetamido-2-deoxy-β-D-glucopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-galactopyranosyl)-thioureido]-decane
  参考文献：
  名称：

  Enzymatic synthesis of dimeric glycomimetic ligands of NK cell activation receptors

  摘要：

  This work reveals new structural relationships in the complex process of the interaction between activation receptors of natural killer cells (rat NKR-P1, human CD69) and novel bivalent carbohydrate glycomimetics. The length, glycosylation pattern and linker structure of receptor ligands were examined with respect to their ability to precipitate the receptor protein from solution, which simulates the in vivo process of receptor aggregation during NK cell activation. It was found that di-LacdiNAc triazole compounds show optimal performance, reaching up to 100% precipitation of the present protein receptors, and achieving high immunostimulatory activities without any tendency to trigger activation-induced apoptosis. In the synthesis of the compounds tested, two enzymatic approaches were applied. Whereas a beta-N-acetylhexosaminidase could only glycosylate one of the two acceptor sites available with yields below 10%, the Y284L mutant of human placental beta 1,4-galactosyltransferase-1 worked as a perfect synthetic tool, accomplishing even quantitative glycosylation at both acceptor sites and with absolute regioselectivity for the C-4 position. This work insinuates new directions for further ligand structure optimisation and demonstrates the strong synthetic potential of the mutant human placental beta 1,4-galactosyltransferase-1 in the synthesis of multivalent glycomimetics and glycomaterials. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2011.04.043

文献信息

• Enzymatic synthesis of dimeric glycomimetic ligands of NK cell activation receptors
  作者：Anna Drozdová、Pavla Bojarová、Karel Křenek、Lenka Weignerová、Birgit Henßen、Lothar Elling、Helle Christensen、Henrik H. Jensen、Helena Pelantová、Marek Kuzma、Karel Bezouška、Monika Krupová、David Adámek、Kristýna Slámová、Vladimír Křen

  DOI：10.1016/j.carres.2011.04.043

  日期：2011.9

  This work reveals new structural relationships in the complex process of the interaction between activation receptors of natural killer cells (rat NKR-P1, human CD69) and novel bivalent carbohydrate glycomimetics. The length, glycosylation pattern and linker structure of receptor ligands were examined with respect to their ability to precipitate the receptor protein from solution, which simulates the in vivo process of receptor aggregation during NK cell activation. It was found that di-LacdiNAc triazole compounds show optimal performance, reaching up to 100% precipitation of the present protein receptors, and achieving high immunostimulatory activities without any tendency to trigger activation-induced apoptosis. In the synthesis of the compounds tested, two enzymatic approaches were applied. Whereas a beta-N-acetylhexosaminidase could only glycosylate one of the two acceptor sites available with yields below 10%, the Y284L mutant of human placental beta 1,4-galactosyltransferase-1 worked as a perfect synthetic tool, accomplishing even quantitative glycosylation at both acceptor sites and with absolute regioselectivity for the C-4 position. This work insinuates new directions for further ligand structure optimisation and demonstrates the strong synthetic potential of the mutant human placental beta 1,4-galactosyltransferase-1 in the synthesis of multivalent glycomimetics and glycomaterials. (C) 2011 Elsevier Ltd. All rights reserved.