2,7-去氢-N-乙酰基神经氨酸 | 95574-95-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 中文名称: 2,7-去氢-N-乙酰基神经氨酸
• 英文名称: 2,7-anhydro-N-acetylneuraminic acid
• 英文别名: 2,7-anhydro-Neu5Ac；N-acetyl-2,7-anhydro-alpha-neuraminic acid；(1R,2R,3S,5S,7R)-2-acetamido-7-[(1R)-1,2-dihydroxyethyl]-3-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid
• CAS: 95574-95-1
• 化学式: C₁₁H₁₇NO₈
• 分子量: 291.258
• InChiKey: NCMJSVDTRDLWJE-YRMXFSIDSA-N

物化性质

• 沸点：
  734.2±60.0 °C(Predicted)
• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2,7-去氢-N-乙酰基神经氨酸 在 recombinant oxidoreductase from Ruminococcus gnavus ATCC 29149 、 还原型辅酶Ⅰ 作用下， 以 aq. phosphate buffer 为溶剂， 生成 N-乙酰神经氨酸
  参考文献：
  名称：

  Uncovering a novel molecular mechanism for scavenging sialic acids in bacteria

  摘要：

  The human gut symbiontRuminococcus gnavusscavenges host-derivedN-acetylneuraminic acid (Neu5Ac) from mucins by converting it to 2,7-anhydro-Neu5Ac. We previously showed that 2,7-anhydro-Neu5Ac is transported intoR. gnavusATCC 29149 before being converted back to Neu5Ac for further metabolic processing. However, the molecular mechanism leading to the conversion of 2,7-anhydro-Neu5Ac to Neu5Ac remained elusive. Using 1D and 2D NMR, we elucidated the multistep enzymatic mechanism of the oxidoreductase (RgNanOx) that leads to the reversible conversion of 2,7-anhydro-Neu5Ac to Neu5Ac through formation of a 4-keto-2-deoxy-2,3-dehydro-N-acetylneuraminic acid intermediate and NAD(+)regeneration. The crystal structure ofRgNanOx in complex with the NAD(+)cofactor showed a protein dimer with a Rossman fold. Guided by theRgNanOx structure, we identified catalytic residues by site-directed mutagenesis. Bioinformatics analyses revealed the presence ofRgNanOx homologues across Gram-negative and Gram-positive bacterial species and co-occurrence with sialic acid transporters. We showed by electrospray ionization spray MS that theEscherichia colihomologue YjhC displayed activity against 2,7-anhydro-Neu5Ac and thatE. colicould catabolize 2,7-anhydro-Neu5Ac. Differential scanning fluorimetry analyses confirmed the binding of YjhC to the substrates 2,7-anhydro-Neu5Ac and Neu5Ac, as well as to co-factors NAD and NADH. Finally, usingE. colimutants and complementation growth assays, we demonstrated that 2,7-anhydro-Neu5Ac catabolism inE. colidepended on YjhC and on the predicted sialic acid transporter YjhB. These results revealed the molecular mechanisms of 2,7-anhydro-Neu5Ac catabolism across bacterial species and a novel sialic acid transport and catabolism pathway inE. coli.

  DOI：

  10.1074/jbc.ra120.014454
• 作为产物：
  描述：

  N-acetyl neuraminic acid 在 CMP-唾液酸合成酶 、 Pasteurella multocida sialyltransferase 1 mutant 、 胞苷-5’-三磷酸 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 反应 4.0h， 生成 2,7-去氢-N-乙酰基神经氨酸
  参考文献：
  名称：

  [EN] SIALIDASE INHIBITORS AND PREPARATION THEREOF
  [FR] INHIBITEURS DE SIALIDASE ET LEUR PRÉPARATION

  摘要：

  公开号：

  WO2018201058A3

文献信息

• A substrate tagging and two-step enzymatic reaction strategy for large-scale synthesis of 2,7-anhydro-sialic acid
  作者：Wanqing Li、Tamashree Ghosh、Yuanyuan Bai、Abhishek Santra、An Xiao、Xi Chen

  DOI：10.1016/j.carres.2019.05.002

  日期：2019.6

  A sialyltransferase acceptor tagging and two-step enzymatic reaction strategy has been developed for multigram-scale chemoenzymatic synthesis of 2,7-anhydro-N-acetylneuraminic acid (2,7-anhydro-Neu5Ac), a compound that can serve as a sole carbon source for the growth of Ruminococcus gnavus, a common human gut commensal. Different approaches of introducing hydrophobic UV-active tags to lactose as well-suited

  已开发了唾液酸转移酶受体标记和两步酶促反应策略，用于多克级化学酶促合成2,7-脱水-N-乙酰神经氨酸（2,7-脱水-Neu5Ac），该化合物可作为唯一的碳鲁米诺球菌（一种常见的人类肠道）的生长来源。已经探索了将疏水性紫外线活性标签引入乳糖作为合适的唾液酸转移酶受体的不同方法，并且已经确定了一种简单的两步高产率化学合成方法。具有紫外线活性的疏水标签有助于监控反应进程，并允许通过C18墨盒轻松纯化产物。已经建立了两步酶催化的反应程序，与基于C18滤芯的纯化工艺相结合，可以以发克级标记的乳糖苷原料和唾液酸中间体中间体的循环使用，以多克规模高产所需产物。这项研究证明了一种环保的高效合成和纯化策略，可用于生产2,7-脱水Neu5Ac，以探索其潜在功能。
• Studies on Sialic Acids. XXX. Synthesis of 2,7-Anhydrosialic Acid.
  作者：Kimio FURUHATA、Haruo OGURA

  DOI：10.1248/cpb.40.3197

  日期：——

  N-Acetyl-and N-glycolyl-2, 7-anhydroneuraminic acid were synthesized from methyl 5-acetamido-3, 5-dideoxy-2-thio-α-D-glycero-D-galacto-2-nonulopyranosonate in high yield. The structures and stereochemistry of these glycosanic sialic acids were elucidated from 1H-NMR spectra and X-ray crystal analysis. The ring systems of N-acetyl- and N-glycolyl-2, 7-anhydroneuraminic acid (1 and 10) were determined to have the same 2C5(D) conformation.

  以 5-acetamido-3, 5-dideoxy-2-thio-α-D-glycero-D-galacto-2-nonulopyranosonate 甲酯为原料，高产率合成了 N-乙酰基-和 N-乙醇酰基-2, 7-脱水神经氨酸。通过 1H-NMR 谱和 X 射线晶体分析阐明了这些聚糖唾液酸的结构和立体化学。 N-乙酰基-和N-乙醇酰-2, 7-脱水神经氨酸（1和10）的环系统被确定具有相同的2C5(D)构象。
• Structural study of a new sialic acid-containing O-specific polysaccharide of Salmonella arizonae O21; formation of anhydro derivatives of neuraminic acid upon treatment with anhydrous hydrogen fluoride
  作者：Evgeny V. Vinogradov、Nikolay A. Paramonov、Yurity A. Knirel、Alexander S. Shashkov、Nikolay K. Kochetkov

  DOI：10.1016/0008-6215(93)80051-f

  日期：1993.4
• [EN] SIALIDASE INHIBITORS AND PREPARATION THEREOF<br/>[FR] INHIBITEURS DE SIALIDASE ET LEUR PRÉPARATION
  申请人：UNIV CALIFORNIA

  公开号：WO2018201058A3

  公开（公告）日：2018-11-29
• Uncovering a novel molecular mechanism for scavenging sialic acids in bacteria
  作者：Andrew Bell、Emmanuele Severi、Micah Lee、Serena Monaco、Dimitrios Latousakis、Jesus Angulo、Gavin H. Thomas、James H. Naismith、Nathalie Juge

  DOI：10.1074/jbc.ra120.014454

  日期：2020.10

  The human gut symbiontRuminococcus gnavusscavenges host-derivedN-acetylneuraminic acid (Neu5Ac) from mucins by converting it to 2,7-anhydro-Neu5Ac. We previously showed that 2,7-anhydro-Neu5Ac is transported intoR. gnavusATCC 29149 before being converted back to Neu5Ac for further metabolic processing. However, the molecular mechanism leading to the conversion of 2,7-anhydro-Neu5Ac to Neu5Ac remained elusive. Using 1D and 2D NMR, we elucidated the multistep enzymatic mechanism of the oxidoreductase (RgNanOx) that leads to the reversible conversion of 2,7-anhydro-Neu5Ac to Neu5Ac through formation of a 4-keto-2-deoxy-2,3-dehydro-N-acetylneuraminic acid intermediate and NAD(+)regeneration. The crystal structure ofRgNanOx in complex with the NAD(+)cofactor showed a protein dimer with a Rossman fold. Guided by theRgNanOx structure, we identified catalytic residues by site-directed mutagenesis. Bioinformatics analyses revealed the presence ofRgNanOx homologues across Gram-negative and Gram-positive bacterial species and co-occurrence with sialic acid transporters. We showed by electrospray ionization spray MS that theEscherichia colihomologue YjhC displayed activity against 2,7-anhydro-Neu5Ac and thatE. colicould catabolize 2,7-anhydro-Neu5Ac. Differential scanning fluorimetry analyses confirmed the binding of YjhC to the substrates 2,7-anhydro-Neu5Ac and Neu5Ac, as well as to co-factors NAD and NADH. Finally, usingE. colimutants and complementation growth assays, we demonstrated that 2,7-anhydro-Neu5Ac catabolism inE. colidepended on YjhC and on the predicted sialic acid transporter YjhB. These results revealed the molecular mechanisms of 2,7-anhydro-Neu5Ac catabolism across bacterial species and a novel sialic acid transport and catabolism pathway inE. coli.