1,4-bis-(3-(2-acetamido-2-deoxy-α-D-glucopyranosyloxycarbonylamino)propoxy)butane | 1233921-19-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,4-bis-(3-(2-acetamido-2-deoxy-α-D-glucopyranosyloxycarbonylamino)propoxy)butane
• 英文别名: [(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl] N-[3-[4-[3-[[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxycarbonylamino]propoxy]butoxy]propyl]carbamate
• CAS: 1233921-19-1
• 化学式: C₂₈H₅₀N₄O₁₆
• 分子量: 698.722
• InChiKey: UGDUEIJNWXKCIS-VCVUPCPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  48
• 可旋转键数：
  21
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  293
• 氢给体数：
  10
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  1,4-bis-(3-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyloxycarbonylamino)propoxy)butane 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 1,4-bis-(3-(2-acetamido-2-deoxy-α-D-glucopyranosyloxycarbonylamino)propoxy)butane
  参考文献：
  名称：

  内联凝集素配体的无沉淀高亲和力多价结合

  摘要：

  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。

  DOI：

  10.1039/d0sc01744b

文献信息

• Structural Basis of Multivalent Binding to Wheat Germ Agglutinin
  作者：David Schwefel、Caroline Maierhofer、Johannes G. Beck、Sonja Seeberger、Kay Diederichs、Heiko M. Möller、Wolfram Welte、Valentin Wittmann

  DOI：10.1021/ja101646k

  日期：2010.6.30

  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.
• 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。