p-nitrophenoxycarbonyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranoside | 1233921-11-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: p-nitrophenoxycarbonyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranoside
• 英文别名: 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-O-p-nitrophenoxycarbonyl-alpha-d-glucopyranose；[(2R,3S,4R,5R,6R)-5-acetamido-3,4-diacetyloxy-6-(4-nitrophenoxy)carbonyloxyoxan-2-yl]methyl acetate
• CAS: 1233921-11-3
• 化学式: C₂₁H₂₄N₂O₁₃
• 分子量: 512.427
• InChiKey: FGAOSGDVQDQRLW-LASHMREHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  199
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  p-nitrophenoxycarbonyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranoside 在 甲醇 、 sodium methylate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  EPR光谱研究多价碳水化合物与蛋白质相互作用的机理

  摘要：

  从远处看：通过自旋标记电子顺磁共振在纳米范围内进行距离测量，为溶液中多价蛋白质-配体相互作用提供了结构证据（参见图片；蛋白质亚基：蓝色/绿色；配体：黑色；自旋标记：黄色圆圈） ，绑定网站：黄色字母）。数据显示了二价配体与凝集素结合的详细情况。

  DOI：

  10.1002/anie.201101074
• 作为产物：
  描述：

  2-deoxy-2-acetamido-3,4,6-tri-O-acetyl-D-glucopyranose 、 对硝基苯基氯甲酸酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以92%的产率得到p-nitrophenoxycarbonyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranoside
  参考文献：
  名称：

  Structural Basis of Multivalent Binding to Wheat Germ Agglutinin

  摘要：

  The inhibition of carbohydrate protein interactions by tailored multivalent ligands is a powerful strategy for the treatment of many human diseases. Crucial for the success of this approach is an understanding of the molecular mechanisms as to how a binding enhancement of a multivalent ligand is achieved. We have synthesized a series of multivalent N-acetylglucosamine (GIcNAc) derivatives and studied their interaction with the plant lectin wheat germ agglutinin (WGA) by an enzyme-linked lectin assay (ELLA) and X-ray crystallography. The solution conformation of one ligand was determined by NMR spectroscopy. Employing a GIcNAc carbamate motif with alpha-configuration and by systematic variation of the spacer length, we were able to identify divalent ligands with unprecedented high WGA binding potency. The best divalent ligand has an IC(50) value of 9.8 mu M (ELLA) corresponding to a relative potency of 2350 (1170 on a valency-corrected basis, i.e., per mol sugar contained) compared to free GIcNAc. X-ray crystallography of the complex of WGA and the second best, closely related divalent ligand explains this activity. Four divalent molecules simultaneously bind to WGA with each ligand bridging adjacent binding sites. This shows for the first time that all eight sugar binding sites of the WGA dimer are simultaneously functional. We also report a tetravalent neoglycopeptide with an IC(50) value of 0.9 mu M being 25 500 times higher than that of GIcNAc (6400 times per contained sugar) and the X-ray structure analysis of its complex with glutaraldehyde-cross-linked WGA. Comparison of the crystal structure and the solution NMR structure of the neoglycopeptide as well as results from the ELLA suggest that the conformation of the glycopeptide in solution is already preorganized in a way supporting multivalent binding to the protein. Our findings show that bridging adjacent protein binding sites by multivalent ligands is a valid strategy to find high-affinity protein ligands and that even subtle changes of the linker structure can have a significant impact on the binding affinity.

  DOI：

  10.1021/ja101646k

文献信息

• Precipitation-free high-affinity multivalent binding by inline lectin ligands
  作者：Philipp Rohse、Sabrina Weickert、Malte Drescher、Valentin Wittmann

  DOI：10.1039/d0sc01744b

  日期：——

  precipitating binding mode. Here, we present a new design of high-potency multivalent ligands featuring an inline arrangement of ligand epitopes with exceptionally high binding affinities in the low nanomolar range. At the same time, we show with a multi-methodological approach that precipitation of the receptor is prevented. We distinguish distinct binding modes of the ligands, in particular we elucidate

  多价配体与蛋白质的相互作用是生物学介导的重要概念，例如信号传导和粘附。多价配体通常具有极大增加的结合亲和力。但是，它们也会引起受体分子的交联，从而导致配体-受体复合物沉淀。由沉淀引起的斑块形成是许多致命疾病的已知特征，其限制了具有沉淀结合模式的多价配体的潜在医学应用。在这里，我们提出了一种新的高效多价配体设计，其特征是配体表位的内联排列，在低纳摩尔范围内具有异常高的结合亲和力。同时，我们采用多方法论方法表明可以防止受体沉淀。我们区分了配体的不同结合方式，特别地，我们阐明了独特的螯合结合模式，其中四个受体结合位点同时被一个多价配体分子桥接。我们为经过充分研究的模型凝集素小麦胚芽凝集素建立的内联多价配体的新设计概念，对于开发作为未来疗法的高效多价抑制剂具有巨大潜力。
• Mechanistic Insight into Nanomolar Binding of Multivalent Neoglycopeptides to Wheat Germ Agglutinin
  作者：Philipp Rohse、Valentin Wittmann

  DOI：10.1002/chem.201600657

  日期：2016.7.4

  and divalent ligands and that conformational preorganization of the ligands by cyclization is not a prerequisite for achieving high binding affinities. The high affinities of the tetravalent ligands rather stem from their ability to form crosslinks between several WGA molecules. The results illustrate that binding affinities and mechanisms are strongly dependent on the used multivalent system which

  多价碳水化合物与蛋白质的相互作用经常参与基本的生物识别过程。因此，多价通常还被用于设计旨在抑制此类过程的高亲和力凝集素配体。在先前的研究（D. Schwefel等人，J。化学会会志。2010，132（8704–8719），我们确定了一种基于四价环肽的配体，对模型凝集素小麦胚芽凝集素（WGA）具有纳摩尔摩尔亲和力。为了揭示与WGA高亲和力结合所需的这种配体的结构特征，我们合成了一系列环状和线性新糖肽，它们的构象自由度以及GlcNAc残基的数量不同。等温滴定热法（ITC），酶联凝集素测定法（ELLA）和动态光散射（DLS）的综合证据表明，四价和二价配体的结合方式不同，并且环化配体的构象预组织并不是形成混合物的先决条件。实现高绑定亲和力。四价配体的高亲和力更源于它们在几个WGA分子之间形成交联的能力。
• Photoswitching Affinity and Mechanism of Multivalent Lectin Ligands
  作者：Uwe Osswald、Johannes Boneberg、Valentin Wittmann

  DOI：10.1002/chem.202200267

  日期：2022.5.11

  An arylazopyrazole-containing divalent ligand was tailored to control multivalent binding to the model lectin wheat germ agglutinin (WGA) by light irradiation. The ligand was designed in such a way that only the E isomer is able to bridge adjacent binding sites of WGA. The two photoisomers show an unprecedentedly high change in binding affinity, as determined by isothermal titration calorimetry and

  一种含有芳基唑吡唑的二价配体被定制为通过光照射控制多价结合模型凝集素小麦胚芽凝集素 (WGA)。配体的设计方式使得只有E异构体能够桥接 WGA 的相邻结合位点。通过等温滴定量热法和不同的结合模式（ E异构体的螯合结合和Z异构体的交联结合）确定，这两种光异构体在结合亲和力方面表现出前所未有的高变化。