hyaluronan

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: hyaluronan
• 英文别名: hyaluronan hexasaccharide；β-D-glucopyranuronyl-(1→3)-β-D-2-acetamido-2-deoxyglucopyranosyl-(1→4)-β-D-glucopyranuronyl-(1→3)-β-D-2-acetamido-2-deoxyglucopyranosyl-(1→4)-β-D-glucopyranuronyl-(1→3)-D-2-acetamido-2-deoxyglucopyranose；(GlcUA-GlcNAc)3；GlcA(b1-3)GlcNAc(b1-4)GlcA(b1-3)GlcNAc(b1-4)GlcA(b1-3)GlcNAc；(2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-acetamido-2-[(2S,3S,4R,5R,6R)-6-[(3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• 化学式: C₄₂H₆₅N₃O₃₄
• 分子量: 1155.98
• InChiKey: LFAUBHLTGUFQPC-PPTIFWKLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -10.9
• 重原子数：
  79
• 可旋转键数：
  19
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  584
• 氢给体数：
  20
• 氢受体数：
  34

反应信息

• 作为反应物：
  描述：

  hyaluronan 在 N-甲基吗啉 、 sodium azide 、 2-chloro-1,3-dimethyl imidazolium chloride 作用下， 以 水 为溶剂， 反应 30.0h， 以48%的产率得到azido O-(β-D-glucopyranosyluronate)-(1→3)-(2-acetamido-2-deoxy-β-D-glucopyranoside)-(1→4)-(β-D-glucopyranosyluronate)-(1→3)-(2-acetamido-2-deoxy-β-D-glucopyranoside)(1→4)-(β-D-glucopyranosyluronate)-(1→3)-(2-acetamido-2-deoxy-β-D-glucopyranoside)
  参考文献：
  名称：

  定义的硫酸化低聚乙酰透明质酸的合成揭示了GAG-蛋白质结合的结构效应，多样性和热力学†

  摘要：

  硫酸化糖胺聚糖（GAG）与多种细胞外调节蛋白的结合对于诸如细胞生长，迁移，组织稳态和修复等生理过程至关重要。因此，GAG衍生物在用于组织再生疗法的创新生物材料的开发中显示出极大的相关性。我们提出了一种合成的策略，用于定义硫酸化的寡聚透明质酸聚糖库，其模型GAG的长度，硫酸化模式和异头取代系统地变化，以阐明这些参数对调节蛋白对GAG识别的影响。通过使用荧光偏振ITC的实验和计算方法，对接和分子动力学模拟，我们研究了这些功能化的GAG衍生物与十种代表性调节蛋白的结合，包括IL-8，IL-10，BMP-2，硬化蛋白，TIMP-3，CXCL-12，TGF-β，FGF-1， FGF-2和AT-III，我们建立了GAG识别的构效关系。绑定主要是由焓驱动的，而熵的贡献很小。在某些情况下，结合是由GAG的长度决定的，在所有情况下都是由硫酸盐的位置和数量决定的。亲和力很大程度上取决于GAG的端基修饰。最高的

  DOI：

  10.1039/c8sc03649g
• 作为产物：
  描述：

  hyaluronic acid 在 bovine testis hyaluronidase 作用下， 以23%的产率得到hyaluronan
  参考文献：
  名称：

  一锅合成未保护的端基糖基巯基巯基乙醇，可与功能化糖进行聚糖连接反应

  摘要：

  寡糖缀合物的化学合成对于研究碳水化合物的功能相关性至关重要，如果可以使用可靠的方法将水中未保护的糖进行异头连接，则将大大简化此任务。本文介绍了一种从复杂的未保护的单糖，二糖和寡糖制备异头糖基硫醇的方法。通过利用2-乙酰氨基基团的邻近基团效应，可以生成1,2-恶唑啉，并通过用1-硫代酸处理将其转化为1-糖基硫代酯。原位释放的未保护的异头糖基硫醇盐与迈克尔受体，脂族卤化物和氮丙啶偶联，以提供通用的糖偶联物。氨基酸和蛋白质的缀合是通过硫醇与末端烯烃的反应完成的。

  DOI：

  10.1002/anie.201607228

文献信息

• Mechanism for the hydrolysis of hyaluronan oligosaccharides by bovine testicular hyaluronidase
  作者：Ikuko Kakizaki、Nobuyuki Ibori、Kaoru Kojima、Masanori Yamaguchi、Masahiko Endo

  DOI：10.1111/j.1742-4658.2010.07600.x

  日期：2010.4

  Synthetic hyaluronan oligosaccharides with defined structures and their pyridylaminated derivatives were used to investigate the mechanism of hydrolysis of hyaluronan by bovine testicular hyaluronidase. The products of the hydrolysis were analyzed by HPLC and ion‐spray mass spectroscopy (MS). It was confirmed that the minimum substrate for bovine testicular hyaluronidase is the hyaluronan hexasaccharide, even though it is a poor substrate that is barely cleaved, even on prolonged incubation. When hyaluronan octasaccharide was the substrate, increasing amounts of tetrasaccharide and hexasaccharide were produced with increasing time of incubation. Whereas disaccharide was not detectable in the reaction mixture by HPLC, MS analysis revealed trace amounts. The data suggest that the enzyme generates a disaccharide intermediate from hyaluronan oligosaccharide, the majority of which is transferred to the nonreducing ends of other oligosaccharides, only traces being released as free disaccharide. When hyaluronan octasaccharide, with an unsaturated glucuronic acid at the nonreducing end, was used as a substrate, only a tetrasaccharide was detected by HPLC. However, MS showed that the product was a mixture of equal amounts of two tetrasaccharides, one with and the other without the unsaturated glucuronic acid. This suggests that, in the case of substrates with a double bond at the nonreducing end, a tetrasaccharide is cleaved off instead of a disaccharide. The results of the experiments with pyridylaminated oligosaccharides were entirely consistent with these conclusions, and in addition showed the importance of the reducing end of the substrate for the enzyme to recognize the length of the saccharide.
• One-Pot Synthesis of Unprotected Anomeric Glycosyl Thiols in Water for Glycan Ligation Reactions with Highly Functionalized Sugars
  作者：Sebastian Köhling、Matthias P. Exner、Saba Nojoumi、Jürgen Schiller、Nediljko Budisa、Jörg Rademann

  DOI：10.1002/anie.201607228

  日期：2016.12.12

  Chemical synthesis of oligosaccharide conjugates is essential for studying the functional relevance of carbohydrates, and this task would be facilitated considerably if reliable methods for the anomeric ligation of unprotected sugars in water were available. Here, a method for the preparation of anomeric glycosyl thiols from complex unprotected mono‐, di‐, and oligosaccharides is presented. By exploiting

  寡糖缀合物的化学合成对于研究碳水化合物的功能相关性至关重要，如果可以使用可靠的方法将水中未保护的糖进行异头连接，则将大大简化此任务。本文介绍了一种从复杂的未保护的单糖，二糖和寡糖制备异头糖基硫醇的方法。通过利用2-乙酰氨基基团的邻近基团效应，可以生成1,2-恶唑啉，并通过用1-硫代酸处理将其转化为1-糖基硫代酯。原位释放的未保护的异头糖基硫醇盐与迈克尔受体，脂族卤化物和氮丙啶偶联，以提供通用的糖偶联物。氨基酸和蛋白质的缀合是通过硫醇与末端烯烃的反应完成的。
• Syntheses of defined sulfated oligohyaluronans reveal structural effects, diversity and thermodynamics of GAG–protein binding
  作者：Sebastian Köhling、Joanna Blaszkiewicz、Gloria Ruiz-Gómez、María Isabel Fernández-Bachiller、Katharina Lemmnitzer、Nydia Panitz、Annette G. Beck-Sickinger、Jürgen Schiller、M. Teresa Pisabarro、Jörg Rademann

  DOI：10.1039/c8sc03649g

  日期：——

  of sulfates. Affinities strongly depend on the anomeric modification of the GAG. Highest binding affinities are effected by anomeric functionalization with large fluorophores and by GAG dimerization. Our experimental and theoretical results suggest that the diversity of GAG binding sites and modes is responsible for the observed high affinities and other binding features. The presented new insights into

  硫酸化糖胺聚糖（GAG）与多种细胞外调节蛋白的结合对于诸如细胞生长，迁移，组织稳态和修复等生理过程至关重要。因此，GAG衍生物在用于组织再生疗法的创新生物材料的开发中显示出极大的相关性。我们提出了一种合成的策略，用于定义硫酸化的寡聚透明质酸聚糖库，其模型GAG的长度，硫酸化模式和异头取代系统地变化，以阐明这些参数对调节蛋白对GAG识别的影响。通过使用荧光偏振ITC的实验和计算方法，对接和分子动力学模拟，我们研究了这些功能化的GAG衍生物与十种代表性调节蛋白的结合，包括IL-8，IL-10，BMP-2，硬化蛋白，TIMP-3，CXCL-12，TGF-β，FGF-1， FGF-2和AT-III，我们建立了GAG识别的构效关系。绑定主要是由焓驱动的，而熵的贡献很小。在某些情况下，结合是由GAG的长度决定的，在所有情况下都是由硫酸盐的位置和数量决定的。亲和力很大程度上取决于GAG的端基修饰。最高的