UDP-glucuronic acid | 1245697-26-0

• 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: UDP-glucuronic acid
• 英文别名: uridine 5'-diphosphoglucuronic acid；uridine diphosphate glucuronic acid；UDP-GlcA；Udpga；(2S,3S,4S,5R)-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
• CAS: 1245697-26-0
• 化学式: C₁₅H₂₂N₂O₁₈P₂
• 分子量: 580.29
• InChiKey: HDYANYHVCAPMJV-MCYVOLKRSA-N

物化性质

• 密度：
  2.05±0.1 g/cm3(Predicted)

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：

  UDP-glucuronic acid 在 1H-咪唑-1-磺酰叠氮盐酸盐 、 copper(ll) sulfate pentahydrate 、 glycosyltransferase from Escherichia coli K₄ strain 、 三乙胺 、 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 48.0h， 生成
  参考文献：
  名称：

  酶法合成均质硫酸软骨素寡糖

  摘要：

  硫酸软骨素（CS）是一种硫酸化的多糖，起着重要的生理作用。在这里，我们报告了一种基于酶的方法，用于合成15种不同的CS寡糖的文库。该文库涵盖从三糖到九糖的4-O-硫酸化和6-O-硫酸化低聚糖。我们还描述了包含6-O-磺基-2-叠氮基半乳糖胺或6-O-磺基半乳糖胺残基的非天然6-O-硫酸化CS五糖的合成。结构上确定的CS寡糖的可用性提供了一种新颖的方法来研究CS的生物学功能。

  DOI：

  10.1002/anie.201705638
• 作为产物：
  描述：

  D-glucuronic acid 1-phosphate 、 尿苷-5'-三磷酸 在 Pisum sativum UDP-sugar pyrophosphorylase 作用下， 生成 UDP-glucuronic acid
  参考文献：
  名称：

  Cloning of Glucuronokinase from Arabidopsis thaliana, the Last Missing Enzyme of the myo-Inositol Oxygenase Pathway to Nucleotide Sugars

  摘要：

  Nucleotide sugars are building blocks for carbohydrate polymers in plant cell walls. They are synthesized from sugar-1-phosphates or epimerized as nucleotide sugars. The main precursor for primary cell walls is UDP-glucuronic acid, which can be synthesized via two independent pathways. One starts with the ring cleavage of myo-inositol into glucuronic acid, which requires a glucuronokinase and a pyrophosphorylase for activation into UDP-glucuronate. Here we report on the purification of glucuronokinase from Lilium pollen. A 40-kDa protein was purified combining six chromatographic steps and peptides were de novo sequenced. This allowed the cloning of the gene from Arabidopsis thaliana and the expression of the recombinant protein in Escherichia coli for biochemical characterization. Glucuronokinase is a novel member of the GHMP-kinase superfamily having an unique substrate specificity for D-glucuronic acid with a K-m of 0.7 mM. It requires ATP as phosphate donor (K-m 0.56 mM). In Arabidopsis, the gene is expressed in all plant tissues with a preference for pollen. Genes for glucuronokinase are present in (all) plants, some algae, and a few bacteria as well as in some lower animals.

  DOI：

  10.1074/jbc.m109.069369
• 作为试剂：
  描述：

  黄体酮 在 phosphate buffer 、 (S)-2-[3]pyridyl-pyrrolidine-1-carboxylic acid amide 、 Α-D-吡喃葡萄糖6-磷酸 、 bovine liver tissue supernatant 、 烟酰胺腺嘌呤双核苷酸磷酸盐 、 UDP-glucuronic acid 作用下， 反应 5.0h， 以4%的产率得到5beta-孕甾烷-3,20-二酮
  参考文献：
  名称：

  Metabolism and conjugation of [4-14C]progesterone by bovine liver and adipose tissues, in vitro

  摘要：

  The ability of bovine liver and fat to metabolize progesterone and also to form glucuronide conjugates with these progestins in vitro was investigated. Tissue supernatants were incubated with [4-14C] progesterone, UDP-glucuronic acid, and a NADPH generating system for 5 hr, at 37 degrees C. Steroids were identified by thin-layer chromatography, high performance liquid chromatography, and recrystallization to a constant specific activity. The total original radioactivity which could not be removed by exhaustive ether extraction (presumptive conjugates) was 44.7 +/- 14.2% in liver, 5.0 +/- 3.6% in subcutaneous fat, and 3.7 +/- 2.2% in kidney fat samples. Progestins identified in liver samples include 5 beta-pregnane-3 alpha, 20 alpha-diol (free and conjugate), 5 beta-pregnane-3 alpha, 20 beta-diol (free and conjugate), 3 alpha-hydroxy-5 beta-pregnan-20-one (free and conjugate), 3 beta-hydroxy-5 beta-pregnan-20-one (free), 5 beta-pregnane-3,20-dione (free), and progesterone (conjugate). Progestins identified in both the free and conjugate fractions of subcutaneous fat and kidney fat samples include progesterone, 3 alpha-hydroxy-5 beta-pregnan-20-one, 20 beta-hydroxy-4-pregnen-3-one, and 20 alpha-hydroxy-4-pregnen-3-one. Differences due to sex of bovine used were noted. These results confirm the ability of bovine liver to readily metabolize progesterone and form glucuronide conjugates of these compounds and suggest that adipose tissues take an active role in these actions in cattle.

  DOI：

  10.1016/0039-128x(82)90041-1

文献信息

• Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches
  作者：Baojian Wu、Xiaoqiang Wang、Shuxing Zhang、Ming Hu

  DOI：10.1007/s11095-012-0666-z

  日期：2012.6

  Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2 = 0.949, r pred 2  = 0.775; CoMSIA: q2 = 0.579, r2 = 0.876, r pred 2  = 0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity.

  通过实验使用145种酚类化合物，并通过3D-QSAR方法分析，确定了人UGT1A9的催化选择性。UGT1A9是一种重要的膜结合酶，催化外源性物质的葡糖醛酸化反应。通过动力学分析确定了UGT1A9的催化效率。使用CoMFA和CoMSIA技术分析了定量结构活性关系。通过将葡糖醛酸化位点及其相邻的芳香环重叠，实现了底物结构的最大立体重叠。对于具有多个活性葡糖醛酸化位点的底物，每个位点被视为单独的底物。3D-QSAR分析产生了统计上可靠的模型，具有良好的预测能力（CoMFA：q2=0.548，r2=0.949，r pred 2=0.775；CoMSIA：q2=0.579，r2=0.876，r pred 2=0.700）。通过轮廓系数图阐明了底物中负责选择性差异的结构特征。将轮廓系数图叠加在UGT1A9的同源模型的催化口袋中，能够高度自信地识别UGT1A9的催化口袋。CoMFA/CoMSIA模型可以预测底物的选择性和UGT1A9的体外清除率。我们的发现还提供了理解UGT1A9功能和底物选择性的可能分子基础。
• Identification of Human UGT2B7 as the Major Isoform Involved in the<i>O</i>-Glucuronidation of Chloramphenicol
  作者：Mei Chen、Barbara LeDuc、Stephen Kerr、David Howe、David A. Williams

  DOI：10.1124/dmd.109.029900

  日期：2010.3

  Chloramphenicol (CP), a broad spectrum antibiotic, is eliminated in humans by glucuronidation. The primary UGT enzymes responsible for CP O -glucuronidation remain unidentified. We have previously identified the 3- O -CP (major) and 1- O -CP (minor) glucuronides by β-glucuronidase hydrolysis, liquid chromatography-tandem mass spectrometry, and 1D/2D H NMR. Reaction phenotyping for the glucuronidation of CP with 12 expressed human liver UGT isoforms has identified UGT2B7 as having the highest activity for 3- O - and 1- O -CP glucuronidation with minor contributions from UGT1A6 and UGT1A9. The kinetics of CP 3- O -glucuronidation by pooled human liver microsomes (HLMs) exhibited biphasic Michaelis-Menten kinetics with the apparent high-affinity K m1 and low-affinity K m2 values of 46.0 and 1027 μM, whereas expressed UGT2B7 exhibited Michaelis-Menten kinetics with the apparent K m value of 109.1 μM. The formation of 1- O -CP glucuronide by pooled HLM and expressed UGT2B7 exhibited substrate inhibition kinetics with apparent K m values of 408.2 and 115.0 μM, respectively. Azidothymidine (AZT) and hyodeoxycholic acid (substrates of UGT2B7) inhibited 3- O - and 1- O -CP glucuronidation in pooled HLMs. In 10 donor HLM preparations, both CP 3- O - and CP 1- O -glucuronidation showed a significant correlation with AZT glucuronidation (UGT2B7) ( r s = 0.85 and r s = 0.83, respectively) at 30 μM CP, whereas no significant correlation was observed between CP 3- O -glucuronidation and serotonin glucuronidation (UGT1A6) or propofol glucuronidation (UGT1A9) at this CP concentration. These results suggest that UGT2B7 is the primary human hepatic UDP-glucuronosyltransferase isoform catalyzing 3- O - and 1- O -CP glucuronidation with minor contributions from UGT1A6 and UGT1A9.

  氯霉素(CP)是一种广谱抗生素,在人体内通过葡糖醛酸化途径被清除。负责CP O-葡糖醛酸化的主要UGT酶仍然未被识别。我们之前通过β-葡糖醛酸苷酶水解、液相色谱-串联质谱和1D/2D 1H NMR鉴定了3-O-CP(主要)和1-O-CP(次要)葡糖醛酸苷。对12种表达的人肝UGT同工酶的CP葡糖醛酸化反应表型进行鉴定,发现UGT2B7对3-O-和1-O-CP葡糖醛酸化活性最高,UGT1A6和UGT1A9有较小贡献。人肝微粒体(HLMs)中CP 3-O-葡糖醛酸化动力学呈双相米氏动力学,高亲和力Km1值和低亲和力Km2值分别为46.0μM和1027μM,而表达的UGT2B7呈现单相米氏动力学,Km值为109.1μM。人肝微粒体和表达的UGT2B7的1-O-CP葡糖醛酸苷形成呈现底物抑制动力学,Km值分别为408.2μM和115.0μM。叠氮胸苷(AZT)和猪胆酸(UGT2B7的底物)抑制了人肝微粒体中的3-O-和1-O-CP葡糖醛酸化。在10个供体的人肝微粒体中,30μM CP时,CP 3-O-和CP 1-O-葡糖醛酸化与AZT葡糖醛酸化(UGT2B7)显著相关(rs=0.85和rs=0.83),而CP 3-O-葡糖醛酸化与5-羟色胺葡糖醛酸化(UGT1A6)或丙泊酚葡糖醛酸化(UGT1A9)在此CP浓度下无显著相关性。这些结果表明,UGT2B7是催化3-O-和1-O-CP葡糖醛酸化的主要人肝UDP-葡糖醛酸基转移酶同工酶,UGT1A6和UGT1A9有较小贡献。
• A general strategy for the synthesis of homogeneous hyaluronan conjugates and their biological applications
  作者：Xuan Fu、Wenjing Shang、Shuaishuai Wang、Yunpeng Liu、Jingyao Qu、Xi Chen、Peng George Wang、Junqiang Fang

  DOI：10.1039/c6cc09431g

  日期：——

  Here, we developed a general strategy for synthesizing homogeneous HA conjugates, and generated homogeneous HA–pNP, HA–biotin, and HA–oroxylin conjugates to investigate the relationships between HA chain length and its diverse biological functions.

  在这里，我们开发了一种合成均质HA偶联物的一般策略，并生成了均质HA-pNP、HA-生物素和HA-oroxylin偶联物，以研究HA链长度与其多种生物功能之间的关系。
• Uridine Diphosphate Glucuronosyltransferase Isoform-Dependent Regiospecificity of Glucuronidation of Flavonoids
  作者：Rashim Singh、Baojian Wu、Lan Tang、Ming Hu

  DOI：10.1021/jf1041454

  日期：2011.7.13

  objective of this study was to determine the regiospecificity of the important uridine diphosphate glucuronosyltransferase (UGT) isoforms responsible for the glucuronidation of flavones and flavonols. We systematically studied the glucuronidation of 13 flavonoids (7 flavones and 6 flavonols, with hydroxyl groups at C-3, C-4′, C-5, and/or C-7 positions in flavonoid structure) at a substrate concentration

  本研究的目的是确定负责黄酮和黄酮醇葡萄糖醛酸化的重要尿苷二磷酸葡萄糖醛酸转移酶 (UGT) 异构体的区域特异性。我们系统地研究了 13 种黄酮类化合物（7 种黄酮和 6 种黄酮醇，在类黄酮结构的 C-3、C-4'、C-5 和/或 C-7 位具有羟基）在 10 μM 底物浓度下的葡萄糖醛酸化由 8 种重组人 UGT 亚型组成，主要负责黄酮类化合物的代谢，UGT 1A1、1A3、1A6、1A7、1A8、1A9、1A10 和 2B7。在 10 μM 底物浓度下，不同的 UGT 同种型产生不同的区域特异性葡萄糖醛酸化模式。UGT 1A1 葡萄糖醛酸化 3- O（葡萄糖醛酸在 C-3 羟基上取代）、7- O和 4'- O，而 UGT 1A8 和 1A9 优选仅对 3- O和 7- O位进行葡糖醛酸化。UGT 1A1 通常对任何位置的葡萄糖醛酸化没有区域特异性，而 UGT 1A8 和 UGT 1A9 对
• ORGANIC COMPOUNDS
  申请人：Hassiepen Ulrich

  公开号：US20100256080A1

  公开（公告）日：2010-10-07

  The present invention relates to a compound The instant invention relates to a compound of formulae (I A), (I B), (X A), (X B), (Y A) or (Y B), wherein R′ represents and R″ represents hydrogen, hydroxy, C 1 -C 7 alkoxy, C 1 -C 8 -alkanoyloxy, or R 5 R 4 N—CO—O—, where R 4 and R 5 independently are C 1 -C 7 alkyl or phenyl which is unsubstituted or substituted by a substitutent selected from C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogen and trifluoromethyl and where R 4 additionally is hydrogen; or R 4 and R 5 together represent C 3 -C 6 alkylene; in free form or in form of a pharmaceutically acceptable acid addition salt. Compounds of formulae (I A), (I B), (X A), (X B), (Y A) or (Y B) inhibit DPP-IV (dipeptidyl-peptidase-IV) activity. They are therefore indicated for use as pharmaceuticals in inhibiting DPP-IV and in the treatment of conditions mediated by DPP-IV, such as non-insulin-dependent diabetes mellitus, arthritis, obesity, osteoporosis and further conditions of impaired glucose tolerance.

  本发明涉及一种化合物。本发明涉及一种具有式(I A)、(I B)、(X A)、(X B)、(Y A)或(Y B)的化合物，其中R′代表，R″代表氢、羟基、C1-C7烷氧基、C1-C8-烷酰氧基，或R5R4N—CO—O—，其中R4和R5独立地为C1-C7烷基或苯基，未取代或被C1-C7烷基、C1-C7烷氧基、卤素和三氟甲基等取代基取代，且R4另外为氢；或者R4和R5共同表示C3-C6烷基链；以自由形式或药学上可接受的酸盐形式存在。式(I A)、(I B)、(X A)、(X B)、(Y A)或(Y B)的化合物抑制DPP-IV（二肽基肽酶-IV）活性。因此，它们适用于作为药物用于抑制DPP-IV和治疗由DPP-IV介导的疾病，如非胰岛素依赖型糖尿病、关节炎、肥胖症、骨质疏松症以及其他葡萄糖耐量受损疾病。