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)thioureido]decane | 1319018-58-0

• 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)thioureido]decane
• 英文别名: 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-glucopyranosyl)-thioureido]-decane；N-[(2R,3R,4R,5S,6R)-2-[10-[[(2R,3R,4R,5S,6R)-3-acetamido-5-[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]carbamothioylamino]decylcarbamothioylamino]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide
• CAS: 1319018-58-0
• 化学式: C₃₆H₆₅N₇O₁₅S₂
• 分子量: 900.082
• InChiKey: YPMOJTXPRMOHNL-JQIMGZLFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  60
• 可旋转键数：
  21
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  398
• 氢给体数：
  15
• 氢受体数：
  17

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 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 28.5h， 生成 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)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

• Chemo-enzymatic synthesis of LacdiNAc dimers of varying length as novel galectin ligands
  作者：Anna Šimonová、Christiane E. Kupper、Sophia Böcker、Alwina Müller、Kateřina Hofbauerová、Helena Pelantová、Lothar Elling、Vladimír Křen、Pavla Bojarová

  DOI：10.1016/j.molcatb.2013.12.018

  日期：2014.3

  A set of sixteen bivalent symmetrical and asymmetrical LacdiNAc dimers containing flexible alkyl linkers were efficiently synthesized by means of chemo-enzymatic synthesis, using the versatile potential of the Y284L mutant of human placental β1,4-galactosyltransferase-1. LacdiNAc was confirmed to be a specific ligand for human galectin-3 contrary to human galectin-1. The compounds were tested as ligands

  利用人胎盘β1,4-半乳糖基转移酶-1的Y284L突变体的多用途潜力，通过化学酶促合成有效地合成了一组十六个包含柔性烷基接头的二价对称和不对称LacdiNAc二聚体。LacdiNAc被证实是与人galectin-1相反的人galectin-3的特异性配体。在竞争性结合试验中，将这些化合物作为人galectin-3的配体进行了测试，并与单价LacdiNAc标准品进行了比较。进行分子建模以计算各个配体的近似长度及其与抑制能力的关系。在携带具有足够的长度（烷基链组成的疏水连接体连接的两个单位的LacdiNAc对称化合物中观察到最佳的性能Ñ  ≥6）。在这里，IC 50值比单价标准低约三倍。我们的研究结果表明，由烷基链长以及LacdiNAc的特异性和双价决定的疏水性有助于这些配体的抑制潜能。尽管在这种情况下仅略微明显，但更高的多价是半乳糖凝集素3优化配体设计的一个有前途的特征。