5-iodouridine-5'-diphosphate-α-D-galactose | 1253736-62-7

• 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: 5-iodouridine-5'-diphosphate-α-D-galactose
• 英文别名: 5-iodo-UDP-α-D-Gal；5-iodo-UDP-α-D-galactose；5-Iodouridine-5'-diphosphate-alpha-D-galactose；[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-iodo-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] hydrogen phosphate
• CAS: 1253736-62-7
• 化学式: C₁₅H₂₃IN₂O₁₇P₂
• 分子量: 692.203
• InChiKey: QCUKWILIHIFMAI-FQKYAJAOSA-N

物化性质

• 密度：
  2.26±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -6
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 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：

  5-iodouridine-5'-diphosphate-α-D-galactose 在 二磷酸酯 、 5-iodouridine-5'-diphosphate-α-D-galactose 、 glucose-1-phosphate uridylyltransferase 、 uridine-5'-diphosphogalactose 4''-epimerase from Erwinia amylovora 作用下， 以 aq. buffer 为溶剂， 反应 2.67h， 生成 5-iodouridine-5'-diphosphate-α-D-N-acetylglucosamine
  参考文献：
  名称：

  Enzymatic synthesis of nucleobase-modified UDP-sugars: scope and limitations

  摘要：

  Glucose-1-phosphate uridylyltransferase in conjunction with UDP-glucose pyrophosphorylase was found to catalyse the conversion of a range of 5-substituted UTP derivatives into the corresponding UDP-galactose derivatives in poor yield. Notably the 5-iodo derivative was not converted to UDP-sugar. In contrast, UDP-glucose pyrophosphorylase in conjunction with inorganic pyrophosphatase was particularly effective at converting 5-substituted UTP derivatives, including the iodo compound, into a range of gluco-configured 5-substituted UDP-sugar derivatives in good yields. Attempts to effect 400-epimerization of these 5-substituted UDP-glucose with UDP-glucose 4 ''-epimerase from yeast were unsuccessful, while use of the corresponding enzyme from Erwinia amylovora resulted in efficient epimerization of only 5-iodo-UDP-Glc, but not the corresponding 5-aryl derivatives, to give 5-iodo-UDP-Gal. Given the established potential for Pd-mediated cross-coupling of 5-iodo-UDP-sugars, this provides convenient access to the galacto-configured 5-substituted-UDP-sugars from gluco-configured substrates and 5-iodo-UTP. (C) 2015 The Authors. Published by Elsevier Ltd.

  DOI：

  10.1016/j.carres.2014.12.005
• 作为产物：
  描述：

  尿苷5-单磷酸 在 碘 、 硝酸 作用下， 以 氯仿 、 二甲基亚砜 为溶剂， 反应 13.08h， 生成 5-iodouridine-5'-diphosphate-α-D-galactose
  参考文献：
  名称：

  [EN] DERIVATIVES OF URIDINE PHOSPHATE AND THEIR USES IN PROTEIN BINDING ASSAYS
  [FR] COMPOSÉS ET LEURS UTILISATIONS DANS DES DOSAGES DE LIAISON AUX PROTÉINES

  摘要：

  公开号：

  WO2011051733A3
• 作为试剂：
  描述：

  5-iodo-UDP-Glc 在 二磷酸酯 、 5-iodouridine-5'-diphosphate-α-D-galactose 、 glucose-1-phosphate uridylyltransferase 作用下， 反应 0.17h， 生成 5-Iodo-UTP
  参考文献：
  名称：

  Enzymatic synthesis of nucleobase-modified UDP-sugars: scope and limitations

  摘要：

  Glucose-1-phosphate uridylyltransferase in conjunction with UDP-glucose pyrophosphorylase was found to catalyse the conversion of a range of 5-substituted UTP derivatives into the corresponding UDP-galactose derivatives in poor yield. Notably the 5-iodo derivative was not converted to UDP-sugar. In contrast, UDP-glucose pyrophosphorylase in conjunction with inorganic pyrophosphatase was particularly effective at converting 5-substituted UTP derivatives, including the iodo compound, into a range of gluco-configured 5-substituted UDP-sugar derivatives in good yields. Attempts to effect 400-epimerization of these 5-substituted UDP-glucose with UDP-glucose 4 ''-epimerase from yeast were unsuccessful, while use of the corresponding enzyme from Erwinia amylovora resulted in efficient epimerization of only 5-iodo-UDP-Glc, but not the corresponding 5-aryl derivatives, to give 5-iodo-UDP-Gal. Given the established potential for Pd-mediated cross-coupling of 5-iodo-UDP-sugars, this provides convenient access to the galacto-configured 5-substituted-UDP-sugars from gluco-configured substrates and 5-iodo-UTP. (C) 2015 The Authors. Published by Elsevier Ltd.

  DOI：

  10.1016/j.carres.2014.12.005

文献信息

• Optimised chemical synthesis of 5-substituted UDP-sugars and their evaluation as glycosyltransferase inhibitors
  作者：Lauren M. Tedaldi、Michael Pierce、Gerd K. Wagner

  DOI：10.1016/j.carres.2012.10.009

  日期：2012.12

  cross-coupling with 5-formylthien-2-ylboronic acid under aqueous conditions. Importantly, 5-iodo UDP-GlcNAc and 5-(5-formylthien-2-yl) UDP-GlcNAc showed moderate inhibitory activity against the GlcNAc transferase GnT-V, providing the first examples for the inhibition of a GlcNAc transferase by a base-modified donor analogue.

  我们研究了焦磷酸键形成的不同化学方法对合成 5-取代 UDP-半乳糖和 UDP-N-乙酰氨基葡萄糖衍生物的适用性。使用磷吗啉化学，结合 N-甲基咪唑氯化物作为促进剂，被认为是制备这些非天然糖核苷酸的最可靠的合成方案。在这些条件下，主要合成目标 5-碘 UDP-半乳糖和 5-碘 UDP-N-乙酰氨基葡萄糖始终以 40-43% 的分离产率获得。两种 5-碘 UDP-糖都成功地用作 Suzuki-Miyaura 在水性条件下与 5-formylthien-2-ylboronic 酸交叉偶联的底物。重要的，
• A Novel Fluorescent Probe for Retaining Galactosyltransferases
  作者：Thomas Pesnot、Monica M. Palcic、Gerd K. Wagner

  DOI：10.1002/cbic.201000013

  日期：——

  A new U: A new fluorescent derivative of UDP‐galactose, modified at the uracil base, is strongly emissive in aqueous solution. The fluorescence emission is quenched upon specific binding at a galactosyltransferase. This effect was exploited for ligand‐displacement experiments with four different enzymes.

  一个新的U：在尿嘧啶碱基上修饰的一种新的UDP-半乳糖的荧光衍生物，在水溶液中强烈发射。在半乳糖基转移酶上特异性结合后，荧光发射被猝灭。这种作用被用于四种不同酶的配体置换实验。
• Inhibition of Galactosyltransferases by a Novel Class of Donor Analogues
  作者：Karine Descroix、Thomas Pesnot、Yayoi Yoshimura、Sebastian S. Gehrke、Warren Wakarchuk、Monica M. Palcic、Gerd K. Wagner

  DOI：10.1021/jm201154p

  日期：2012.3.8

  Galactosyltransferases (GalT) are important molecular targets in a range of therapeutic areas, including infection, inflammation, and cancer. GalT inhibitors are therefore sought after as potential lead compounds for drug discovery. We have recently discovered a new class of GalT inhibitors with a novel mode of action. In this publication, we describe a series of analogues which provide insights, for the first time, into SAR for this new mode of GalT inhibition. We also report that a new C-glycoside, designed as a chemically stable analogue of the most potent inhibitor in this series, retains inhibitory activity against a panel of GalTs. Initial results from cellular studies suggest that despite their polarity, these sugar-nucleotides are taken up by HL-60 cells. Results from molecular modeling studies with a representative bacterial GalT provide a rationale for the differences in bioactivity observed in this series. These findings may provide a blueprint for the rational development of new GalT inhibitors with improved potency.