uridine diphosphoglucuronic acid

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: uridine diphosphoglucuronic acid
• 英文别名: uridine 5'-diphosphoglucuronic acid；uridine diphosphate glucuronic acid；UDP-glucuronic acid；(2S,3S,4S,5R,6S)-6-[[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• 化学式: C₁₅H₂₂N₂O₁₈P₂
• 分子量: 580.29
• InChiKey: HDYANYHVCAPMJV-MGHJJKLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.4
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  309
• 氢给体数：
  9
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  uridine diphosphoglucuronic acid 在 Escherichia coli glycosyltransferase 、 Pasteurella multocida heparan synthase 、 manganese(ll) chloride 作用下， 以 aq. buffer 为溶剂， 生成
  参考文献：
  名称：

  Fluorous-Assisted Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides

  摘要：

  The chemoenzymatic synthesis of heparan sulfate tetrasaccharide (1) and hexasaccharide (2) with a fluorous tag. attached at the reducing end is reported. The fluorous tert-butyl dicarbonate ((F)Boc) tag did not interfere with enzymatic recognition for both elongation and specific sulfation, and flash purification was performed by standard fluorous solid-phase extraction (FSPE). Based on an (F)Boc attached disaccharide as acceptor, a series of partial N-sulfated, 6-O-sulfated heparan sulfate. oligosaccharides were successfully synthesized employing fluorous techniques.

  DOI：

  10.1021/ol500738g
• 作为产物：
  描述：

  UDP-glucose 在 Glycyrrhiza uralensis UDP-glucose dehydrogenase 、 nicotinamide adenine dinucleotide 作用下， 反应 12.0h， 生成 uridine diphosphoglucuronic acid
  参考文献：
  名称：

  甘草（Glycyrrhiza uralensis）UDP-葡萄糖脱氢酶的功能表征和底物混杂性分析

  摘要：

  尿苷二磷酸葡萄糖脱氢酶（UGDH）在UDP-葡萄糖醛酸（UDPGA）的合成中起关键作用，UDP-葡萄糖醛酸是中药甘草中生物活性三萜皂苷葡萄糖醛酸基化的重要糖供体。UGDH 通常作为同种型存在于植物中，但对其独特结合位点和模式的了解在很大程度上仍然不完整。在这里，我们在G. uralensis中挖掘了五种 UGDH 亚型催化 UDP-葡萄糖 (UDPG) 氧化为 UDPGA 并具有不同催化效率的转录组。分子建模和分子动力学模拟揭示了异构体催化效率的潜在催化残基。此外，UGDH 异构体通过催化两种结构不同的 UDPG 衍生物表现出底物混杂性，对接研究进一步证明了这一点。这项工作对参与G. uralensis中葡糖苷酸生物合成的 UGDH 亚型提供了新的见解，并扩展了对 UGDH 多功能性的理解。

  DOI：

  10.1016/j.molstruc.2022.133355

文献信息

• Facile chemoenzymatic synthesis of biotinylated heparosan hexasaccharide
  作者：Baolin Wu、Na Wei、Vireak Thon、Mohui Wei、Zaikuan Yu、Yongmei Xu、Xi Chen、Jian Liu、Peng George Wang、Tiehai Li

  DOI：10.1039/c5ob00462d

  日期：——

  A biotinylated heparosan hexasaccharide was synthesized by a facile chemoenzymatic approach in a one-pot multi-enzyme fashion.

  通过一种简便的化学酶法，以一锅多酶的方式合成了生物素化的肝素六糖。
• Synthesis of morphine-6-glucuronide via a highly selective enzyme catalysed hydrolysis reaction
  作者：Richard T. Brown、Neil E. Carter、Feodor Scheinmann、Nicholas J. Turner

  DOI：10.1016/0040-4039(94)02409-5

  日期：1995.2

  Morphine-6-glucuronide 1, a potent analgesic, has been prepared from morphine-3,6-diglucuronide 3via a highly selective hydrolytic cleavage of the phenolic 3-glucuronide group using β-glucuronidase as catalyst.

  吗啡-6-葡糖苷酸1，一种强效镇痛药，已经从吗啡-3,6- diglucuronide制备3通过使用酚-3-葡糖苷酸基团的高度选择性水解裂解β葡萄糖醛酸酶作为催化剂。
• Uridine diphosphate sugar-selective conjugation of an aldose reductase inhibitor (AS-3201) by UDP-glucuronosyltransferase 2B subfamily in human liver microsomes
  作者：Kenji Toide、Yoshiaki Terauchi、Toshihiko Fujii、Hiroshi Yamazaki、Tetsuya Kamataki

  DOI：10.1016/j.bcp.2003.11.010

  日期：2004.4

  each UGT isoform to the N-glucosidation in human liver microsomes. The results showed that UGT2B isoforms mainly contribute to AS-3201 N-glucosidation in human liver microsomes. In addition, the activity of AS-3201 N-glucosyltransferase significantly correlated with that of amobarbital N-glucosyltransferase in microsomes from sixteen human livers (r=0.964, P<0.01), indicating that UGT2B isoforms were also

  N-葡萄糖苷化被认为是人类巴比妥类药物的主要代谢反应。但是，尚未弄清参与该N-葡萄糖苷化的酶。因此，为弄清参与人肝微粒体中N-葡萄糖苷化的酶，我们使用醛糖还原酶抑制剂AS-3201作为底物，研究了重组UDP-葡萄糖醛酸糖基转移酶（UGT）中的N-葡萄糖基转移酶活性。发现AS-3201在人肝微粒体中被生物转化为N-葡萄糖苷和N-葡萄糖醛酸苷。N-葡萄糖基转移酶活性可通过多种UGT亚型（UGT1A1，UGT1A3，UGT1A4，UGT2B4，UGT2B7和UGT2B15）检测到。相比之下，使用UGT1A（UGT1A1，UGT1A3，UGT1A4和UGT1A9）观察到相同底物的N-葡萄糖醛酸转移酶活性，但未观察到UGT2B亚型。然后，我们确定了每个重组UGT的相对活性因子，并估计了每个UGT亚型对人肝微粒体中N-葡萄糖苷化的贡献。结果表明，UGT2B亚型主要促进人肝微粒体中AS-3201的N-葡
• Chemoenzymatic synthesis and structural characterization of 2-O-sulfated glucuronic acid-containing heparan sulfate hexasaccharides
  作者：Po-Hung Hsieh、Yongmei Xu、David A Keire、Jian Liu

  DOI：10.1093/glycob/cwu032

  日期：2014.8.1

  Heparan sulfate and heparin are highly sulfated polysaccharides that consist of a repeating disaccharide unit of glucosamine and glucuronic or iduronic acid. The 2-O-sulfated iduronic acid (IdoA2S) residue is commonly found in heparan sulfate and heparin; however, 2-O-sulfated glucuronic acid (GlcA2S) is a less abundant monosaccharide (∼<5% of total saccharides). Here, we report the synthesis of three GlcA2S-containing hexasaccharides using a chemoenzymatic approach. For comparison purposes, additional IdoA2S-containing hexasaccharides were synthesized. Nuclear magnetic resonance analyses were performed to obtain full chemical shift assignments for the GlcA2S- and IdoA2S-hexasaccharides. These data show that GlcA2S is a more structurally rigid saccharide residue than IdoA2S. The antithrombin (AT) binding affinities of a GlcA2S- and an IdoA2S-hexasaccharide were determined by affinity co-electrophoresis. In contrast to IdoA2S-hexasaccharides, the GlcA2S-hexasaccharide does not bind to AT, confirming that the presence of IdoA2S is critically important for the anticoagulant activity. The availability of pure synthetic GlcA2S-containing oligosaccharides will allow the investigation of the structure and activity relationships of individual sites in heparin or heparan sulfate.

  硫酸肝素和肝素是高度硫酸化的多糖，由葡萄糖胺和葡萄糖醛酸或艾杜糖醛酸的重复二糖单元组成。2-O-硫酸化的艾杜糖醛酸（IdoA2S）残基在硫酸肝素和肝素中常见；然而，2-O-硫酸化的葡萄糖醛酸（GlcA2S）是一种较为稀少的单糖（约占糖总量的<5%）。在这里，我们报告了使用化学酶法合成了三种含有GlcA2S的六糖。为了比较，还合成了额外的含有IdoA2S的六糖。通过核磁共振分析获得了含有GlcA2S和IdoA2S的六糖的完整化学位移分配。这些数据表明GlcA2S是一种比IdoA2S结构更刚性的糖残基。通过亲和共电泳测定了含有GlcA2S和IdoA2S的六糖与抗凝血酶（AT）的结合亲和力。与含有IdoA2S的六糖不同，含有GlcA2S的六糖不与AT结合，证实IdoA2S的存在对于抗凝活性至关重要。纯合成含有GlcA2S的低聚糖的可获得性将允许研究肝素或硫酸肝素中各个位点的结构与活性关系。
• Regioselective Glucuronidation of Flavonols by Six Human UGT1A Isoforms
  作者：Baojian Wu、Beibei Xu、Ming Hu

  DOI：10.1007/s11095-011-0418-5

  日期：2011.8

  Glucuronidation is a major barrier to flavonoid bioavailability; understanding its regiospecificity and reaction kinetics would greatly enhance our ability to model and predict flavonoid disposition. We aimed to determine the regioselective glucuronidation of four model flavonols using six expressed human UGT1A isoforms (UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10). In vitro reaction kinetic profiles of six UGT1A-mediated metabolism of four flavonols (all with 7-OH group) were characterized; kinetic parameters (Km, Vmax and CLint = Vmax/Km) were determined. UGT1A1 and 1A3 regioselectively metabolized the 7-OH group, whereas UGT1A7, 1A8, 1A9 and 1A10 preferred to glucuronidate the 3-OH group. UGT1A1 and 1A9 were the most efficient conjugating enzymes with Km values of ≤1 μM and relative catalytic efficiency ratios of ≥5.5. Glucuronidation by UGT1As displayed surprisingly strong substrate inhibition. In particular, Ksi values (substrate inhibition constant) were less than 5.4 μM for UGT1A1-mediated metabolism. UGT1A isoforms displayed distinct positional preferences between 3-OH and 7-OH of flavonols. Differentiated kinetic properties between 3-O- and 7-O- glucuronidation suggested that (at least) two distinct binding modes within the catalytic domain were possible. The existence of multiple binding modes should provide better “expert” knowledge to model and predict UGT1A-mediated glucuronidation.

  葡萄糖醛酸化是类黄酮生物利用度的主要障碍；了解其区域选择性和反应动力学会大大增强我们建模和预测类黄酮处置的能力。我们的目标是确定四种模型二苯乙烯酮在六种表达的人类UGT1A同工酶（UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10）作用下的区域选择性葡萄糖醛酸化。表征了六种UGT1A介导的四种二苯乙烯酮（均含7-OH基团）的体外反应动力学曲线；确定了动力学参数（Km, Vmax和CLint = Vmax/Km）。UGT1A1和1A3区域选择性地代谢7-OH基团，而UGT1A7, 1A8, 1A9和1A10更倾向于对3-OH基团进行葡萄糖醛酸化。UGT1A1和1A9是最有效的结合酶，其Km值≤1 μM，相对催化效率比≥5.5。UGT1A的葡萄糖醛酸化显示出惊人的强底物抑制作用。特别是，UGT1A1介导的代谢的Ksi值（底物抑制常数）小于5.4 μM。UGT1A同工酶显示出对二苯乙烯酮的3-OH和7-OH的不同位置偏好。3-O-和7-O-葡萄糖醛酸化的区分动力学特性表明（至少）催化域内存在两种不同的结合模式。多种结合模式的存在应提供更好的“专家”知识来建模和预测UGT1A介导的葡萄糖醛酸化。