[(2R,3S,4R,5R)-5-(2-氨基-6-氧代-3,6-二氢-9H-嘌呤-9-基)-3,4-二羟基四氢-2-呋喃基]甲基(2R,3S,4S,5S,6R)-3,4,5-三羟基-6-甲基四氢-2H-吡喃-2-基二氢二磷酸酯 | 15839-74-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 中文名称: [(2R,3S,4R,5R)-5-(2-氨基-6-氧代-3,6-二氢-9H-嘌呤-9-基)-3,4-二羟基四氢-2-呋喃基]甲基(2R,3S,4S,5S,6R)-3,4,5-三羟基-6-甲基四氢-2H-吡喃-2-基二氢二磷酸酯
• 英文名称: GDP-D-Rha
• 英文别名: Guanosine-5'-diphosphate-rhamnose；[[(2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-methyloxan-2-yl] hydrogen phosphate
• CAS: 15839-74-4
• 化学式: C₁₆H₂₅N₅O₁₅P₂
• 分子量: 589.347
• InChiKey: LQEBEXMHBLQMDB-GDJBGNAASA-N

物化性质

• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -5.7
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  307
• 氢给体数：
  9
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  [(2S,3S,4R,5R)-5-(2-氨基-6-氧代-3H-嘌呤-9-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基-[[(2R,3R,4S,6S)-3,4-二羟基-6-甲基-5-氧代-四氢吡喃-2-基]氧基-羟基-磷酰]氧基-次磷酸 在 葡萄糖 、 β-烟酰胺腺嘌呤二核苷酸 、 C-4 reductase from Pseudomonas aeruginosa 、 glycoside hydrolase 作用下， 以 aq. buffer 为溶剂， 以2.73 g的产率得到[(2R,3S,4R,5R)-5-(2-氨基-6-氧代-3,6-二氢-9H-嘌呤-9-基)-3,4-二羟基四氢-2-呋喃基]甲基(2R,3S,4S,5S,6R)-3,4,5-三羟基-6-甲基四氢-2H-吡喃-2-基二氢二磷酸酯
  参考文献：
  名称：

  通过级联转换策略从普通糖中轻松合成糖核苷酸

  摘要：

  糖核苷酸是碳水化合物代谢中必不可少的糖基化供体。自然地，大多数糖核苷酸通过从头生物合成途径衍生自有限数量的常见糖核苷酸，经历单一或多重反应，例如脱水、差向异构化、异构化、氧化、还原、胺化和乙酰化反应。然而，人们普遍认为，由于制备成本高且产品分离难度大，这种复杂的生物转化对于合成用途并不实用。因此，大多数发现的糖核苷酸都不容易获得。在这里，基于de novo主要是生物合成，从两种常见的糖 D-Man 和蔗糖中成功制备了 13 种难以获得的糖核苷酸，其产量高达数克，无需繁琐的纯化操作。这项工作表明，从头生物合成虽然经历了复杂的反应，但通过采用级联转换策略，对于合成使用也是实用且具有成本效益的。

  DOI：

  10.1021/jacs.2c03138

文献信息

• Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from <i>Salmonella enterica</i>
  作者：Lu Zou、Ruixiang Blake Zheng、Todd L Lowary

  DOI：10.3762/bjoc.8.136

  日期：——

  A series of methoxy and deoxy derivatives of mannopyranose-1-phosphate (Manp-1P) were chemically synthesized, and their ability to be converted into the corresponding guanosine diphosphate mannopyranose (GDP-Manp) analogues by a pyrophosphorylase (GDP-ManPP) from Salmonella enterica was studied. Evaluation of methoxy analogues demonstrated that GDP-ManPP is intolerant of bulky substituents at the C-2, C-3, and C-4 positions, in turn suggesting that these positions are buried inside the enzyme active site. Additionally, both the 6-methoxy and 6-deoxy Manp-1P derivatives are good or moderate substrates for GDP-ManPP, thus indicating that the C-6 hydroxy group of the Manp-1P substrate is not required for binding to the enzyme. When taken into consideration with other previously published work, it appears that this enzyme has potential utility for the chemoenzymatic synthesis of GDP-Manp analogues, which are useful probes for studying enzymes that employ this sugar nucleotide as a substrate.

  一系列甲氧基和去氧衍生物的甘霖糖吡喷酸酯（Manp-1P）经化学合成，研究了它们通过一种来自沙门氏菌（Salmonella enterica）的焦磷酸化酶（GDP-ManPP）能否转化为相应的鸟苷二磷酸甘霖糖（GDP-Manp）类似物的能力。对甲氧基类似物的评价表明，GDP-ManPP对C-2、C-3和C-4位置的庞大取代基不耐受，进而暗示这些位置被埋藏在酶活性位点内部。此外，6-甲氧基和6-去氧 Manp-1P 衍生物均是GDP-ManPP的良好或中等底物，因此表明 Manp-1P 底物的C-6 羟基不是与酶结合所必需的。综合考虑先前发表的其他研究成果，这种酶似乎具有潜在的用途，可用于化酶合成 GDP-Manp 类似物，这些类似物是用于研究以这种糖核苷酸为底物的酶的有用探针。
• Mechanism and Active Site Residues of GDP-Fucose Synthase
  作者：Stephen T. B. Lau、Martin E. Tanner

  DOI：10.1021/ja807799k

  日期：2008.12.24

  L-Fucose, 6-deoxy-L-galactose, is a key component of many important glycoconjugates including the blood group antigens and the Lewis(x) ligands. The biosynthesis of GDP-L-fucose begins with the action of a dehydratase that converts GDP-D-mannose into GDP-4-keto-6-deoxy-mannose. The enzyme GDPfucose synthase, GFS, (also known as GDP-4-keto-6-deoxy-D-mannose epimerase/reductase, GMER) then converts GDP-4-keto-6-deoxy-D-mannose into GDP-L-fucose. The GFS reaction involves epimerizations at both C-3 '' and C-5 '' followed by an NADPH-dependent reduction of the carbonyl at C-4. This manuscript describes studies that elucidate the order of the epimerization steps and the roles of the active site acid/base residues responsible for the epimerizations. An active site mutant, Cys109Ser, produces GDP-6-deoxy-D-altrose as its major product indicating that C-3 '' epimerization occurs first and premature reduction of the GDP-4-keto-6-deoxy-D-altrose intermediate becomes competitive with GDP-L-fucose production. The same mutation results in the appearance of a kinetic isotope effect when [3 ''-H-2]-GDP-6-deoxy-4-keto-mannose is used as a substrate. This indicates that Cys109 is the base responsible for the deprotonation of the substrate at C-3 ''. The Cys109Ser mutant also catalyzes a rapid wash-in of solvent derived deuterium into the C-5 '' position of GDP-fucose in the presence of NADP(+). This confirms the order of epimerizations and the role of Cys109. Finally, the inactive His179Gln mutant readily catalyzes the wash-out of deuterium from the C-3 '' position of [3 ''-H-2]-GDP-6-deoxy-4-keto-mannose. Together these results strongly implicate an ordered sequence of epimerizations (C-3 '' followed by C-5 '') and suggest that Cys109 acts as a base and His179 acts as an acid in both epimerization steps.