UDP-Galf | 26097-62-1

• 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-Galf
• 英文别名: UDP-alpha-D-galactofuranose；[(2R,3R,4R,5S)-5-[(1R)-1,2-dihydroxyethyl]-3,4-dihydroxyoxolan-2-yl] [[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate
• CAS: 26097-62-1
• 化学式: C₁₅H₂₄N₂O₁₇P₂
• 分子量: 566.306
• InChiKey: ZQLQOXLUCGXKHS-SIAUPFDVSA-N

物化性质

• 密度：
  1.97±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -6.6
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  292
• 氢给体数：
  9
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  UDP-Galf 在 FAD-dependent UDP-Galp-mutase 、 reconstituted by 1-deaza-FAD 作用下， 以 phosphate buffer 、 甘油 为溶剂， 反应 0.03h， 生成 尿苷 5’-二二氧磷基半乳糖二钠盐
  参考文献：
  名称：

  用1-deaza-FAD和5-deaza-FAD重建UDP-吡喃半乳糖突变酶：分析和机理研究。

  摘要：

  在微生物的许多表面成分中发现的半乳糖呋喃糖部分是通过FAD依赖性UDP-Galp突变酶催化的独特环收缩反应从UDP-D-吡喃半乳糖（UDP-Galp）衍生而来的。当该酶被连二亚硫酸钠还原时，其催化效率显着提高。由于总体转化过程中所涉及的各方的氧化还原状态没有任何净变化，因此酶结合的FAD在反应机理中如何发挥积极作用令人费解。在本文中，我们报告了我们对用deaza-FAD重构的UDP-Galp突变酶的催化性能的研究。发现用FAD或1-deazaFAD重构的突变酶具有相当的活性，而用5-deazaFAD重构的突变酶具有催化活性。由于5-deazaFAD仅限于净二电子过程，但是FAD和1-deazaFAD可以同时发生两电子协同的单电子氧化还原反应，以上结果支持了突变酶催化反应的自由基机理。另外，发现在高pH下用FAD重构的突变酶的活性显着增加。这些观察结果使我们提出了一种新的机制，该机制涉及从还

  DOI：

  10.1016/j.bioorg.2003.08.002
• 作为产物：
  描述：

  尿苷5-单磷酸 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 UDP-Galf
  参考文献：
  名称：

  The first chemical synthesis of UDP-α-D-galactofuranose

  摘要：

  尿苷5'-二磷酸α-D-半乳糖呋喃糖，可能是自然界中D-半乳糖呋喃糖残基的生物化学供体，由α-D-半乳糖呋喃糖磷酸和尿苷5'-单磷酸合成。

  DOI：

  10.1039/b000210k

文献信息

• Studies of UDP-Galactopyranose Mutase from <i>Escherichia </i><i>coli</i>:  An Unusual Role of Reduced FAD in Its Catalysis
  作者：Qibo Zhang、Hung-wen Liu

  DOI：10.1021/ja001333z

  日期：2000.9.1

  study this transformation, the corresponding E. coli mutase was purified, and the ring contraction product, UDP-Galf, was chemically synthesized. Using UDP-Galf as the substrate, a Km of 194 μM and a kcat of 1.5 s-1 for the catalysis in the reverse direction were obtained. The preference of the reaction toward the pyranose product was confirmed by an equilibrium constant of 0.057 in the forward direction

  在微生物的许多表面成分中发现的呋喃半乳糖部分来自 UDP-d-吡喃半乳糖 (UDP-Galp)，通过 UDP-Galp 变位酶催化的独特环收缩反应。这种酶是从多种细菌来源中分离出来的，是一种黄素蛋白，其中 FAD 辅酶是非共价结合的。由于其催化似乎不涉及氧化还原机制，酶结合的FAD是否在反应机制中发挥积极作用一直不清楚。为了研究这种转化，纯化了相应的大肠杆菌变位酶，并化学合成了环收缩产物 UDP-Galf。使用UDP-Galf作为底物，反方向催化得到194 μM的Km和1.5 s-1的kcat。反应对吡喃糖产物的偏好由正向平衡常数 0.057 证实。有趣的是，当酶被连二亚硫酸钠还原后，其催化效率提高了超过...
• Stereoselective Chemoenzymatic Synthesis of UDP-1,2-<i>cis</i>-furanoses from α,β-Furanosyl 1-Phosphates
  作者：Pauline Peltier、Jean-Paul Guégan、Richard Daniellou、Caroline Nugier-Chauvin、Vincent Ferrières

  DOI：10.1002/ejoc.200800742

  日期：2008.12

  broad substrate specificity of this particular enzyme. The chemical synthesis of the needed furanosyl 1-phosphate starting materials was then performed with unprotected thioimidoyl donors. This led to the first stereoselective chemoenzymatic syntheses of UDP-β-L-arabinofuranose, UDP-α-D-fucofuranose and UDP-α-D-6F-galactofuranose from starting mixtures of sugar-phosphates.(© Wiley-VCH Verlag GmbH & Co

  含呋喃糖基的糖缀合物的生物合成描述甚少，主要是由于缺乏 UDP-呋喃糖。在这里，我们展示了我们在多酶系统的帮助下合成稀有核苷酸糖的努力，特别是包括 1-磷酸半乳糖尿苷转移酶。首先，STD-NMR 技术被用来探测这种特定酶的广泛底物特异性。然后用未保护的硫亚氨基供体进行所需的呋喃糖基 1-磷酸起始材料的化学合成。这导致了 UDP-β-L-阿拉伯呋喃糖、UDP-α-D-岩藻呋喃糖和 UDP-α-D-6F-呋喃半乳糖的首次立体选择性化学酶促合成。 （© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
• Synthesis and Analysis of Substrate Analogues for UDP-Galactopyranose Mutase:  Implication for an Oxocarbenium Ion Intermediate in the Catalytic Mechanism
  作者：Kenji Itoh、Zhishu Huang、Hung-wen Liu

  DOI：10.1021/ol0631408

  日期：2007.3.1

  UDP-D-galactofuranose ( 2), which is essential for both cell growth and virulence in many pathogenic microorganisms, is converted from UDP-D-galactopyranose (UDP-Galp, 1) by the flavin adenine dinucleotide (FAD)-dependent enzyme UDP-galactopyranose mutase (UGM). Here, we report the synthesis of UDP-GalOH ( 13) and show it as an inhibitor for UGM with a binding affinity similar to that of 1. These results are more consistent with a mechanism involving an oxocarbenium ion intermediate in UGM catalysis.
• Structural Basis of Ligand Binding to UDP-Galactopyranose Mutase from <i>Mycobacterium tuberculosis</i> Using Substrate and Tetrafluorinated Substrate Analogues
  作者：Karin E. van Straaten、Jijin R. A. Kuttiyatveetil、Charlotte M. Sevrain、Sydney A. Villaume、Jesús Jiménez-Barbero、Bruno Linclau、Stéphane P. Vincent、David A. R. Sanders

  DOI：10.1021/ja511204p

  日期：2015.1.28

  UDP-Galactopyranose mutase (UGM) is a flavin-containing enzyme that catalyzes the reversible conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) and plays a key role in the biosynthesis of the mycobacterial cell wall galactofuran. A soluble, active form of UGM from Mycobacterium tuberculosis (MtUGM) was obtained from a dual His6-MBP-tagged MtUGM construct. We present the first complex structures of MtUGM with bound substrate UDP-Galp (both oxidized flavin and reduced flavin). In addition, we have determined the complex structures of MtUGM with inhibitors (UDP and the dideoxy-tetrafluorinated analogues of both UDP-Galp (UDP-F-4-Galp) and UDP-Galf (UDP-F-4-Galf)), which represent the first complex structures of UGM with an analogue in the furanose form, as well as the first structures of dideoxy-tetrafluorinated sugar analogues bound to a protein. These structures provide detailed insight into ligand recognition by MtUGM and show an overall binding mode similar to those reported for other prokaryotic UGMs. The binding of the ligand induces conformational changes in the enzyme, allowing ligand binding and active-site closure. In addition, the complex structure of MtUGM with UDP-F-4-Galf reveals the first detailed insight into how the furanose moiety binds to UGM. In particular, this study confirmed that the furanoside adopts a high-energy conformation (E-4) within the catalytic pocket. Moreover, these investigations provide structural insights into the enhanced binding of the dideoxy-tetrafluorinated sugars compared to unmodified analogues. These results will help in the design of carbohydrate mimetics and drug development, and show the enormous possibilities for the use of polyfluorination in the design of carbohydrate mimetics.
• Isoprenoid Phosphonophosphates as Glycosyltransferase Acceptor Substrates
  作者：Mario A. Martinez Farias、Virginia A. Kincaid、Venkatachalam R. Annamalai、Laura L. Kiessling

  DOI：10.1021/ja500622v

  日期：2014.6.18

  Glycosyltransferases that act on polyprenol pyrophosphate substrates are challenging to study because their lipid-linked substrates are difficult to isolate from natural sources and arduous to synthesize. To facilitate access to glycosyl acceptors, we assembled phosphonophosphate analogues and showed these are effective substrate surrogates for GlfT1, the essential product of mycobacterial gene Rv3782. Under chemically defined conditions, the galactofuranosyltransferase GlfT1 catalyzes the formation of a tetrasaccharide sequence en route to assembly of the mycobacterial galactan.