D-甘油醛3-磷酸酯 | 591-57-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: D-甘油醛3-磷酸酯
• 英文名称: D-glyceraldehyde-3-phosphate
• 英文别名: glyceraldehyde-3-phosphate；G3P；D-GAP；[(2R)-2-hydroxy-3-oxopropyl] dihydrogen phosphate
• CAS: 591-57-1
• 化学式: C₃H₇O₆P
• 分子量: 170.059
• InChiKey: LXJXRIRHZLFYRP-VKHMYHEASA-N

物化性质

• 沸点：
  399.2±52.0 °C(Predicted)
• 密度：
  1.721±0.06 g/cm3(Predicted)
• 物理描述：
  Solid
• 碰撞截面：
  135.86 Ų [M+H]+ [CCS Type: DT, Method: stepped-field]

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 储存条件：
  -20°C，密封保存于干燥处。

制备方法与用途

甘油醛-3-磷酸（D-Glyceraldehyde 3-phosphate），是一种常见的生物分子，是糖酵解和糖异生过程中的重要中间体，也是卡尔文循环产生的糖类产物。此外，甘油醛-3-磷酸还参与色氨酸和硫胺素的生物合成。

反应信息

• 作为反应物：
  描述：

  D-甘油醛3-磷酸酯 在 Potato acid phosphatase (Pase) 作用下， 以 水 为溶剂， 以85%的产率得到D-(+)-甘油醛
  参考文献：
  名称：

  Synthesis of sugars by aldolase-catalyzed condensation reactions

  摘要：

  DOI：

  10.1021/jo00167a012
• 作为产物：
  描述：

  (R)-glycidaldehyde diethyl acetal 在 disodium hydrogenphosphate 作用下， 反应 26.0h， 生成 D-甘油醛3-磷酸酯
  参考文献：
  名称：

  Deoxyribose-5-phosphate aldolase as a synthetic catalyst

  摘要：

  DOI：

  10.1021/ja00161a064
• 作为试剂：
  描述：

  (2,3,4-三羟基-5-氧代戊基)磷酸二氢酯 、 果糖-6-磷酸 在 D-甘油醛3-磷酸酯 、 E_. coli transketolase 、 recombinant (E_. coli K-12) D-sedoheptulose-7-phosphate isomerase 、 recombinant A. thermoaerophilus [α-C(1)OH specific] D-glycero-D-manno-heptose-7-P kinase 、 焦磷酸硫胺素 、 adenosine 5'-triphosphate disodium salt 、 magnesium chloride 作用下， 以84%的产率得到D-glycero-D-manno-heptopyranose 1α,7-bisphosphate
  参考文献：
  名称：

  Divergence of Biochemical Function in the HAD Superfamily: d-glycero-d-manno-Heptose-1,7-bisphosphate Phosphatase (GmhB)

  摘要：

  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.

  DOI：

  10.1021/bi902018y

文献信息

• Structure-Based mutagenesis approaches toward expanding the substrate specificity of d-2-Deoxyribose-5-phosphate aldolase
  作者：Grace DeSantis、Junjie Liu、David P Clark、Andreas Heine、Ian A Wilson、Chi-Huey Wong

  DOI：10.1016/s0968-0896(02)00429-7

  日期：2003.1

  2-Deoxyribose-5-phosphate aldolase (DERA, EC 4.1.2.4) catalyzes the reversible aldol reaction between acetaldehyde and D-glyceraldehyde-3-phosphate to generate D-2-deoxyribose-5-phosphate. It is unique among the aldolases as it catalyzes the reversible asymmetric aldol addition reaction of two aldehydes. In order to expand the substrate scope and stereoselectivity of DERA, structure-based substrate design as well

  2-脱氧核糖5-磷酸醛缩酶（DERA，EC 4.1.2.4）催化乙醛和D-甘油醛-3-磷酸之间的可逆醛醇缩合反应，生成D-2-脱氧核糖-5-磷酸。它在醛缩酶中是独特的，因为它催化两个醛的可逆不对称醛醇加成反应。为了扩大DERA的底物范围和立体选择性，已经研究了基于结构的底物设计以及位点特异性突变。以DERA的1.05 A晶体结构及其天然底物为指导，设计了5个定点突变体，以提高其与非天然非磷酸化底物D-2-脱氧核糖的活性。其中，在2-脱氧核糖的逆醛醇缩合反应中，S238D变体比野生型酶表现出2.5倍的改善。有趣的是 该S238D突变酶显示在连续的不对称醛醇缩合反应中以3-叠氮基丙醛为底物形成脱氧叠氮基乙基吡喃糖，它是相应内酯和降胆固醇剂立普妥的前体。该叠氮醛不是野生型酶的底物。新的非磷酸化底物的另一种基于结构的设计集中在使用野生型或S238D变体作为催化剂，2-甲基取代醛作为底物的对映体选择
• carba Nicotinamide Adenine Dinucleotide Phosphate: Robust Cofactor for Redox Biocatalysis
  作者：Ioannis Zachos、Manuel Döring、Georg Tafertshofer、Robert C. Simon、Volker Sieber

  DOI：10.1002/anie.202017027

  日期：2021.6.21

  Here we report a new robust nicotinamide dinucleotide phosphate cofactor analog (carba-NADP+) and its acceptance by many enzymes in the class of oxidoreductases. Replacing one ribose oxygen with a methylene group of the natural NADP+ was found to enhance stability dramatically. Decomposition experiments at moderate and high temperatures with the cofactors showed a drastic increase in half-life time

  在这里，我们报告了一种新的强大的烟酰胺二核苷酸磷酸辅因子类似物（carba-NADP +）及其被氧化还原酶类中的许多酶所接受。研究发现，用天然 NADP +的亚甲基取代一个核糖氧可显着增强稳定性。使用辅因子在中温和高温下进行的分解实验表明，高温下的半衰期急剧增加，因为它显着不利于吡啶鎓-N-糖苷键的水解。总体而言，成功测试了超过 27 种不同的氧化还原酶，并给出了全面的分析表征和比较。辅因子 carba-NADP +开辟了恶劣条件下氧化还原生物催化领域。
• Determination of the Activity of 1-Deoxy-d-Xylulose 5-Phosphate Synthase by Pre-column Derivatization-HPLC Using 1,2-Diamino-4,5-Methylenedioxybenzene as a Derivatizing Reagent
  作者：Yan-Fei Liang、Hui Liu、Heng Li、Wen-Yun Gao

  DOI：10.1007/s10930-019-09816-9

  日期：2019.4.15

  α-Ketoacids can be determined by HPLC through pre-column derivatization with 1,2-diamino-4,5-methylenedioxybenzene (DMB) as a derivatizing reagent. Using this method, the specific activity and the steady-state kinetic of 1-deoxy-d-xylulose-5-phosphate synthase (DXS) were measured. Firstly, DXS substrate pyruvate was derivatized with DMB in acidic solution; then the corresponding quinoxalinone was elucidated

  α-酮酸可通过HPLC通过以1,2-二氨基-4,5-亚甲基二氧基苯（DMB）作为衍生试剂的柱前衍生来确定。使用这种方法，1-脱氧-d的比活和稳态动力学测定了-木酮糖-5-磷酸合酶（DXS）。首先，在酸性溶液中用DMB衍生化DXS底物丙酮酸；然后通过LC–ESI–MS阐明相应的喹喔啉酮，并通过HPLC-UV进行定量。最佳衍生化条件如下：pH值为1.0的水性介质，反应温度为80°C，反应时间为60分钟，DMB与丙酮酸的摩尔比为10：1。用甲醇和水的混合物（60：40，v / v）作为流动相，通过等度洗脱进行HPLC。该方法的检出限和线性相关范围分别为0.05 µM和0.002-1.0 mM（R = 0.994）。六次测定的相对标准偏差（RSD）为2.48％。用该方法测定的丙酮酸DXS的稳态动力学参数与报道的数据相同。
• DXP Synthase-Catalyzed CN Bond Formation: Nitroso Substrate Specificity Studies Guide Selective Inhibitor Design
  作者：Francine Morris、Ryan Vierling、Lauren Boucher、Jürgen Bosch、Caren L. Freel Meyers

  DOI：10.1002/cbic.201300187

  日期：2013.7.22

  Put a ring on it: Selective inhibition of DXP synthase is a challenge in developing anti‐infectives targeting isoprenoid biosynthesis. DXP synthase preferentially turns over sterically demanding aryl nitroso substrates to form CN bonds, thus suggesting a new design for unnatural bisubstrate analogues as selective inhibitors of isoprenoid biosynthesis.

  戴上戒指：选择性抑制 DXP 合酶是开发针对类异戊二烯生物合成的抗感染药物的挑战。DXP 合酶优先翻转空间要求高的芳基亚硝基底物以形成 C  N 键，因此提出了一种新设计，将非天然双底物类似物用作类异戊二烯生物合成的选择性抑制剂。
• Targeting DXP synthase in human pathogens: enzyme inhibition and antimicrobial activity of butylacetylphosphonate
  作者：Jessica M Smith、Nicole V Warrington、Ryan J Vierling、Misty L Kuhn、Wayne F Anderson、Andrew T Koppisch、Caren L Freel Meyers

  DOI：10.1038/ja.2013.105

  日期：2014.1

  The unique methylerythritol phosphate pathway for isoprenoid biosynthesis is essential in most bacterial pathogens. The first enzyme in this pathway, 1-deoxy-D-xylulose 5-phosphate (DXP) synthase, catalyzes a distinct thiamin diphosphate (ThDP)-dependent reaction to form DXP from D-glyceraldehyde 3-phosphate (D-GAP) and pyruvate and represents a potential anti-infective drug target. We have previously demonstrated that the unnatural bisubstrate analog, butylacetylphosphonate (BAP), exhibits selective inhibition of Escherichia coli DXP synthase over mammalian ThDP-dependent enzymes. Here, we report the selective inhibition by BAP against recombinant DXP synthase homologs from Mycobacterium tuberculosis, Yersinia pestis and Salmonella enterica. We also demonstrate antimicrobial activity of BAP against both Gram-negative and Gram-positive strains (including E. coli, S. enterica and Bacillus anthracis), and several clinically isolated pathogens. Our results suggest a mechanism of action involving inhibition of DXP synthase and show that BAP acts synergistically with established antimicrobial agents, highlighting a potential strategy to combat emerging resistance in bacterial pathogens.

  独特的甲基赤藓醇磷酸通路对于异戊二烯的生物合成在大多数细菌病原体中是必需的。该通路中的第一个酶—1-脱氧-D-木酮糖-5-磷酸(DXP)合酶，催化一个特异的硫胺素焦磷酸(ThDP)依赖的反应，由D-甘油醛-3-磷酸(D-GAP)和丙酮酸形成DXP，是潜在的抗感染药物靶标。我们之前已经证明，非天然双底物类似物丁基乙酰磷酸盐(BAP)对大肠杆菌DXP合酶具有选择性抑制作用，而对哺乳动物ThDP依赖性酶无明显影响。本文报道了BAP对结核分枝杆菌、鼠疫耶尔森菌和肠炎沙门氏菌的重组DXP合酶同源物的选择性抑制作用。我们还证明了BAP对革兰氏阴性和阳性菌株(包括大肠杆菌、肠炎沙门氏菌和炭疽芽胞杆菌)以及几种临床分离的病原体具有抗菌活性。我们的研究结果表明其作用机制涉及DXP合酶的抑制，并且BAP与已建立的抗菌药物具有协同作用，突出了一种对抗细菌病原体新兴耐药性的潜在策略。