β-D-glucose 1,6-bisphosphate | 52795-15-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: β-D-glucose 1,6-bisphosphate
• 英文别名: 1,6-Di-O-Phosphono-Beta-D-Glucopyranose；[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(phosphonooxymethyl)oxan-2-yl] dihydrogen phosphate
• CAS: 52795-15-0
• 化学式: C₆H₁₄O₁₂P₂
• 分子量: 340.117
• InChiKey: RWHOZGRAXYWRNX-DVKNGEFBSA-N

物化性质

• 沸点：
  733.2±70.0 °C(Predicted)
• 密度：
  2.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  203
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  β-D-glucose 1-phosphate 在 Mg-ATP 、 4-羟乙基哌嗪乙磺酸 作用下， 以 aq. phosphate buffer 为溶剂， 以Ca. 40 mg的产率得到β-D-glucose 1,6-bisphosphate
  参考文献：
  名称：

  β-Glucose-1,6-Bisphosphate Stabilizes Pathological Phophomannomutase2 Mutants In Vitro and Represents a Lead Compound to Develop Pharmacological Chaperones for the Most Common Disorder of Glycosylation, PMM2-CDG

  摘要：

  大量引起PMM2-CDG的突变，PMM2-CDG是最常见的糖基化紊乱，使磷酸甘露糖异构酶2不稳定。我们寻找一种药理伴侣来治疗PMM2-CDG，从磷酸甘露糖异构酶2的天然配体α葡萄糖-1,6-二磷酸的结构开始。化合物β-葡萄糖-1,6-二磷酸通过31P-NMR合成和表征。β-葡萄糖-1,6-二磷酸在体外与其靶酶结合。这种结合诱导了一个大的构象变化，由PELE程序预测，并通过有限蛋白水解在体内验证。使用热稳定性分析测量了β-葡萄糖-1,6-二磷酸稳定野生型磷酸甘露糖异构酶2以及常见的致病突变体的能力。β-葡萄糖-1,6-二磷酸相对抗拒专门水解天然醣二磷酸的酶。

  DOI：

  10.3390/ijms20174164

文献信息

• Wässrige synthetische Organextrakte
  申请人：SCHÜLKE & MAYR GMBH

  公开号：EP0552516A1

  公开（公告）日：1993-07-28

  Die Erfindung betrifft wäßrige, synthetischen Organextrakte, welche mindestens das jeweilige Wirkungsspektrum eines entsprechenden Naturstoffextraktes aufweisen sowie deren Verwendung zur Herstellung kosmetischer und medizinischer Präparate.

  本发明涉及至少具有相应天然物质提取物活性谱的水性合成器官提取物，以及它们在生产化妆品和药用制剂中的用途。
• Divergence of Biochemical Function in the HAD Superfamily: <scp>d</scp>-<i>glycero</i>-<scp>d</scp><i>-manno-</i>Heptose-1,7-bisphosphate Phosphatase (GmhB)
  作者：Liangbing Wang、Hua Huang、Henry H. Nguyen、Karen N. Allen、Patrick S. Mariano、Debra Dunaway-Mariano

  DOI：10.1021/bi902018y

  日期：2010.2.16

  D-glycero-D-manno-Heptose-1,7-bisphosphate phosphatase (GmhB) is a member of the histidinol-phosphate phosphatase (HisB) subfamily of the haloalkanoic acid dehalogenase (HAD) enzyme superfamily. GmhB supports two divergent biochemical pathways in bacteria: the D-glycero-D-manno-heptose-1 alpha-GDP pathway (in S-layer glycoprotein biosynthesis) and the L-glycero-D-manno-heptose-1 beta-ADP pathway (in lipid A biosynthesis). Herein, we report the comparative analysis Of Substrate recognition in selected GmhB orthologs. The substrate specificity of the L-glycero-D-manno-heptose-1 beta-ADP pathway GmhB from Escherichia coli K-12 was evaluated using hexose and heptose bisphosphates, histidinol phosphate, and common organophosphate metabolites. Only D-glycero-D-manno-heptose 1 beta,7-bisphosphate (k(cat)/k(m) = 7 x 10(6) M-1 s(-1)) and D-glycero-D-manno-heptose 1 alpha,7-bisphosphate (k(cat)/K-m, = 7 x 10(4) M-1 s(-1)) displayed physiologically significant Substrate activity. P-31 NMR analysis demonstrated that E. coli GmhB selectively removes the C(7) phosphate. Steady-state kinetic inhibition studies showed that D-glycero-D-manno-heptose 1 beta-phosphate (K-is = 60 mu M, and K-ii = 150 mu M) and histidinol phosphate (K-is = 1 mM, and K-ii = 6 mM), while not hydrolyzed, do in fact bind to E. coli GmhB, which leads to the conclusion that nonproductive binding contributes to substrate discrimination. High catalytic efficiency and a narrow substrate range are characteristic of a well-evolved metabolic enzyme, and as such, E. coli GmhB is set apart from most HAD phosphatases (which are typically inefficient and promiscuous). The specialization of the biochemical function of GmhB was examined by measuring the kinetic constants for hydrolysis of the alpha- and beta-anomers of D-glycero-D-manno-heptose 1 beta,7-bisphosphate catalyzed by the GmhB orthologs of the L-glycero-D-manno- 1 beta-ADP pathways operative in Bordetella bronchiseptica and Mesorhizobium and by the GmhB of the D-glycero-D-manno-heptose 1 alpha-GDP pathway operative in Bacteroides thetaiotaomicron. The results show that although each of these representatives possesses physiologically significant catalytic activity toward both anomers, each displays substantial anomeric specificity. Like E. coli GmhB, B. bronchiseptica GmhB and M. loti GmhB prefer the beta-anomer, whereas B. thetaiotaomicron GmhB is selective for the alpha-anomer. By determining the anomeric configuration of the physiological Substrate (D-glycero-D-manno-heptose 1,7- for each of the four GmhB orthologs, we discovered that the anomeric specificity of GmhB correlates with that of the pathway kinase. The conclusion drawn from this finding is that the evolution of the ancestor to GmhB in the HisB subfamily provided for specialization toward two distinct biochemical functions.
• Posternak, Journal of Biological Chemistry, 1949, vol. 180, p. 1269,1272
  作者：Posternak

  DOI：——

  日期：——
• Leloir et al., Anales des la Asociacion Quimica Argentina, 1949, vol. 37, p. 187,189, 190
  作者：Leloir et al.

  DOI：——

  日期：——
• β-Glucose-1,6-Bisphosphate Stabilizes Pathological Phophomannomutase2 Mutants In Vitro and Represents a Lead Compound to Develop Pharmacological Chaperones for the Most Common Disorder of Glycosylation, PMM2-CDG
  作者：Maria Monticelli、Ludovica Liguori、Mariateresa Allocca、Giuseppina Andreotti、Maria Vittoria Cubellis

  DOI：10.3390/ijms20174164

  日期：——

  A large number of mutations causing PMM2-CDG, which is the most frequent disorder of glycosylation, destabilize phosphomannomutase2. We looked for a pharmacological chaperone to cure PMM2-CDG, starting from the structure of a natural ligand of phosphomannomutase2, α-glucose-1,6-bisphosphate. The compound, β-glucose-1,6-bisphosphate, was synthesized and characterized via 31P-NMR. β-glucose-1,6-bisphosphate binds its target enzyme in silico. The binding induces a large conformational change that was predicted by the program PELE and validated in vitro by limited proteolysis. The ability of the compound to stabilize wild type phosphomannomutase2, as well as frequently encountered pathogenic mutants, was measured using thermal shift assay. β-glucose-1,6-bisphosphate is relatively resistant to the enzyme that specifically hydrolyses natural esose-bisphosphates.

  大量引起PMM2-CDG的突变，PMM2-CDG是最常见的糖基化紊乱，使磷酸甘露糖异构酶2不稳定。我们寻找一种药理伴侣来治疗PMM2-CDG，从磷酸甘露糖异构酶2的天然配体α葡萄糖-1,6-二磷酸的结构开始。化合物β-葡萄糖-1,6-二磷酸通过31P-NMR合成和表征。β-葡萄糖-1,6-二磷酸在体外与其靶酶结合。这种结合诱导了一个大的构象变化，由PELE程序预测，并通过有限蛋白水解在体内验证。使用热稳定性分析测量了β-葡萄糖-1,6-二磷酸稳定野生型磷酸甘露糖异构酶2以及常见的致病突变体的能力。β-葡萄糖-1,6-二磷酸相对抗拒专门水解天然醣二磷酸的酶。