(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl](313C)oxane-2-carboxylic acid | 288301-85-9

• 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: (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl](313C)oxane-2-carboxylic acid
• CAS: 288301-85-9
• 化学式: C₂₀H₃₁N₄O₁₆P
• 分子量: 615.446
• InChiKey: TXCIAUNLDRJGJZ-QKVVMOMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.7
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  321
• 氢给体数：
  10
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl](313C)oxane-2-carboxylic acid 在 α-2,6-sialyl transferase 、 micromonospora veridifaciens sialidase 、 水 、 bovine serum albumin 作用下， 生成
  参考文献：
  名称：

  绿色小单孢菌唾液酸酶催化水解的去糖基化会限制周转率：Michaelis 复合物的构象意义

  摘要：

  基于核心结构 7-(5-acetamido-3,5-dideoxy-d-glycero-α-d-galacto-non-2-ulopyranosylonic acid)-(2→6) 的一组七种同位素取代的唾液酸苷天然底物类似物)-β-D-吡喃半乳糖氧基)-8-氟-4-甲基香豆素 (1, Neu5Acα2,6GalβFMU) 已被合成并用于探测 M. viridifaciens 唾液酸酶转换的限速步骤。环氧 ((18)V)、离去基团氧 ((18)V)、异头碳 ((13)V)、C3-碳 ((13) V)、C3-R 氘 ((D)V(R))、C3-S 氘 ((D)V(S)) 和 C3-双氘 ((D)(2)V) 为 0.986 ± 0.003、1.003分别为 ± 0.005、1.021 ± 0.006、1.001 ± 0.008、1.029 ± 0.007、0.891 ± 0.008 和 0.890

  DOI：

  10.1021/ja109199p
• 作为产物：
  描述：

  N-acetyl neuraminic acid 在 四氮唑 、 叔丁基过氧化氢 、 高氯酸 、 phosphate buffer 、 二甲基硫 、 Dowex-50W-X₈ (H⁺) 、 sodium methylate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 L-lactate dehydrogenase 作用下， 以 甲醇 、 乙醇 、 水 、 甲苯 、 乙腈 、 苯 为溶剂， 反应 76.16h， 生成 (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl](313C)oxane-2-carboxylic acid
  参考文献：
  名称：

  一种在完整糖蛋白上精确化学酶合成 13C 标记的唾液酸寡糖的方法：一种新的单锅 [3-13C]-标记唾液酸类似物的方法，通过控制可逆醛缩酶反应，酶促合成 [3-13C]糖蛋白上的-NeuAc-α-(2→3)-[U-13C]-Gal-β-(1→4)-GlcNAc-β-序列及其构象分析

  摘要：

  A one-pot enzymatic C-13-labeling method for the 3-position of sialic acid (NeuAc) analogues has been developed using NeuAc aldolase, lactate dehydrogenase (LDH), alcohol dehydrogenase (ADI-T), and nucleotide pyrophosphatase (NPP). This method consists of two steps, the first of which is degradation to 2-acetamido-2-deoxy-D-mannose (ManNAc) analogues. This degradation reaction was accelerated by a cofactor regeneration system which converts pyruvic acid into lactic acid using LDH, ADH, and beta-nicotinamide adenine dinucleotide oxidized form (beta-NAD(+)). The second step is condensation of the ManNAc analogue with [3-C-13]-pyruvic acid newly added after decomposition of the cofactor by nucleotide pyrophosphatase which play a role like switch to stop conversion of pyruvic acid into lactic acid. Five different NeuAc analogues have been labeled in good yields using this newly developed one-pot enzymatic procedure. Following conversion of [3-C-13]-NeuAc to CMP-[3-C-13]-NeuAc, enzymatic synthesis of [3-C-13]-NeuAc-alpha-(2-->3)-[U-C-13]-Gal-beta-(1-->4)-GlcNAc-beta-x-ovalbumin (x: hybrid type oligosaccharide) 23 and [3-C-13]-NeuAc-alpha-(2-->3)-[U-C-13]-Gal-beta-(1-->4)-GlcNAc-beta-OMe 26 (sialyl LacNAc) was performed using bovine beta-1,4-galactosyltransferase and rat recombinant alpha-2,3-sialyltransferase. The H-1 chemical shifts of all protons in [3-C-13]-NeuAc-alpha-(2-->3)-[U-C-13]-Gal-beta- on a glycoprotein were assigned by 2D HMQC, 1D HSQC-TOCSY, and the herein described 1D and 2D HSQC-TOCSY-NOESY-TOCSY method. More specifically, the 7-, 8-, and 9-protons of NeuAc could be observed by this HSQC-TOCSY-NOESY-TOCSY method even with only a single C-13 atom at the 3-position. In addition, 1D and 2D HMQC-NOESY spectra as well as carbon spin-lattice relaxation times (T-1) were measured to compare the conformational properties and dynamic behavior of the sialylgalactoside as part of the sialyl LacNAc 26 and when bound to a glycoprotein 23. These analyses suggested that the conformational properties of sialyl LacNAc are similar for both the conjugated and unconjugated forms, and that the torsional angle of the sialyl linkage, i.e., COOH-C2(NeuAc)-O-C3(Gal), is biased toward the anti (-146.7 degrees) conformation. In addition, the flexibility of galactosyl ring when bound to a glycoprotein appears to be significantly restricted by the attachment of NeuAc as compared with unconjugated sialyl LacNAc.

  DOI：

  10.1021/ja994211j

文献信息

• Turnover Is Rate-Limited by Deglycosylation for Micromonospora viridifaciens Sialidase-Catalyzed Hydrolyses: Conformational Implications for the Michaelis Complex
  作者：Jefferson Chan、April Lu、Andrew J. Bennet

  DOI：10.1021/ja109199p

  日期：2011.3.9

  effects (KIEs) on k(cat) for the ring oxygen ((18)V), leaving group oxygen ((18)V), anomeric carbon ((13)V), C3-carbon ((13)V), C3-R deuterium ((D)V(R)), C3-S deuterium ((D)V(S)), and C3-dideuterium ((D)(2)V) are 0.986 ± 0.003, 1.003 ± 0.005, 1.021 ± 0.006, 1.001 ± 0.008, 1.029 ± 0.007, 0.891 ± 0.008, and 0.890 ± 0.006, respectively. The solvent deuterium KIE ((D(2)O)V) for the sialidase-catalyzed hydrolysis

  基于核心结构 7-(5-acetamido-3,5-dideoxy-d-glycero-α-d-galacto-non-2-ulopyranosylonic acid)-(2→6) 的一组七种同位素取代的唾液酸苷天然底物类似物)-β-D-吡喃半乳糖氧基)-8-氟-4-甲基香豆素 (1, Neu5Acα2,6GalβFMU) 已被合成并用于探测 M. viridifaciens 唾液酸酶转换的限速步骤。环氧 ((18)V)、离去基团氧 ((18)V)、异头碳 ((13)V)、C3-碳 ((13) V)、C3-R 氘 ((D)V(R))、C3-S 氘 ((D)V(S)) 和 C3-双氘 ((D)(2)V) 为 0.986 ± 0.003、1.003分别为 ± 0.005、1.021 ± 0.006、1.001 ± 0.008、1.029 ± 0.007、0.891 ± 0.008 和 0.890
• An Approach to the Precise Chemoenzymatic Synthesis of ¹³C-Labeled Sialyloligosaccharide on an Intact Glycoprotein:  A Novel One-Pot [3-¹³C]-Labeling Method for Sialic Acid Analogues by Control of the Reversible Aldolase Reaction, Enzymatic Synthesis of [3-¹³C]-NeuAc-α-(2→3)-[U-¹³C]-Gal-β-(1→4)-GlcNAc-β- Sequence onto Glycoprotein, and Its Conformational Analysis by Developed NMR Techniques
  作者：Tatsuo Miyazaki、Hajime Sato、Tohru Sakakibara、Yasuhiro Kajihara

  DOI：10.1021/ja994211j

  日期：2000.6.1

  A one-pot enzymatic C-13-labeling method for the 3-position of sialic acid (NeuAc) analogues has been developed using NeuAc aldolase, lactate dehydrogenase (LDH), alcohol dehydrogenase (ADI-T), and nucleotide pyrophosphatase (NPP). This method consists of two steps, the first of which is degradation to 2-acetamido-2-deoxy-D-mannose (ManNAc) analogues. This degradation reaction was accelerated by a cofactor regeneration system which converts pyruvic acid into lactic acid using LDH, ADH, and beta-nicotinamide adenine dinucleotide oxidized form (beta-NAD(+)). The second step is condensation of the ManNAc analogue with [3-C-13]-pyruvic acid newly added after decomposition of the cofactor by nucleotide pyrophosphatase which play a role like switch to stop conversion of pyruvic acid into lactic acid. Five different NeuAc analogues have been labeled in good yields using this newly developed one-pot enzymatic procedure. Following conversion of [3-C-13]-NeuAc to CMP-[3-C-13]-NeuAc, enzymatic synthesis of [3-C-13]-NeuAc-alpha-(2-->3)-[U-C-13]-Gal-beta-(1-->4)-GlcNAc-beta-x-ovalbumin (x: hybrid type oligosaccharide) 23 and [3-C-13]-NeuAc-alpha-(2-->3)-[U-C-13]-Gal-beta-(1-->4)-GlcNAc-beta-OMe 26 (sialyl LacNAc) was performed using bovine beta-1,4-galactosyltransferase and rat recombinant alpha-2,3-sialyltransferase. The H-1 chemical shifts of all protons in [3-C-13]-NeuAc-alpha-(2-->3)-[U-C-13]-Gal-beta- on a glycoprotein were assigned by 2D HMQC, 1D HSQC-TOCSY, and the herein described 1D and 2D HSQC-TOCSY-NOESY-TOCSY method. More specifically, the 7-, 8-, and 9-protons of NeuAc could be observed by this HSQC-TOCSY-NOESY-TOCSY method even with only a single C-13 atom at the 3-position. In addition, 1D and 2D HMQC-NOESY spectra as well as carbon spin-lattice relaxation times (T-1) were measured to compare the conformational properties and dynamic behavior of the sialylgalactoside as part of the sialyl LacNAc 26 and when bound to a glycoprotein 23. These analyses suggested that the conformational properties of sialyl LacNAc are similar for both the conjugated and unconjugated forms, and that the torsional angle of the sialyl linkage, i.e., COOH-C2(NeuAc)-O-C3(Gal), is biased toward the anti (-146.7 degrees) conformation. In addition, the flexibility of galactosyl ring when bound to a glycoprotein appears to be significantly restricted by the attachment of NeuAc as compared with unconjugated sialyl LacNAc.