UDP-4-amino sugar | 877466-28-9

• 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: UDP-4-amino sugar
• 英文别名: uridine 5′-diphosphate-2,4,6-trideoxy-2-acetamido-4-aminoglucose；UDP-2-acetamido-4-amino-2,4,6-trideoxy-alpha-D-glucose；[(2R,3R,4S,5S,6R)-3-acetamido-5-amino-4-hydroxy-6-methyloxan-2-yl] [[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate
• CAS: 877466-28-9
• 化学式: C₁₇H₂₈N₄O₁₅P₂
• 分子量: 590.375
• InChiKey: FUUMLYWEEZBCQR-UINYWEPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -8.7
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  286
• 氢给体数：
  8
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  UDP-4-amino sugar 在 disodium hydrogenphosphate 、 Campylobacter jejuni hexa-His-tagged PglD acetyltransferase 、 Escherichia coli NanA sialic acid aldolase 、 Legionella pneumophila NeuC hydrolyzing 2-epimerase 、 三羟甲基氨基甲烷盐酸盐 、 magnesium chloride 作用下， 以 水 为溶剂， 反应 51.0h， 生成 5,7-diacetamido-3,5,7,9-tetradeoxy-D-glycero-β-D-galactonon-2-ulosonic acid
  参考文献：
  名称：

  Enzymatic synthesis and properties of glycoconjugates with legionaminic acid as a replacement for neuraminic acid

  摘要：

  除硅醛酸外，细菌还产生其他几种非乌洛托品酸，包括军团酰胺酸（Leg）。这种酸的立体化学结构与硅藻酸完全相同，但增加了 9-脱氧基团和 7-氨基基团。为了探索用 Leg 的双乙酰化形式--双乙酰军团胺酸（Leg5Ac7Ac）--取代糖醛酸残基（Neu5Ac）对生物的影响，我们用细菌和哺乳动物的部分硅烷基转移酶测试了 CMP-Leg5Ac7Ac 作为供体底物的效果。CMP-Leg5Ac7Ac 是通过克隆空肠弯曲杆菌 N-聚糖途径中的巴基氨基部分和嗜肺军团菌途径中的酶在体外合成的。我们使用乳糖的荧光衍生物、Galβ1,4GlcNAcβ和T-抗原（Galβ1,3GalNAcα）作为受体，测试了八种不同的硅烷基转移酶，发现多杀性巴氏杆菌 PM0188h 和猪 ST3Gal1 硅烷基转移酶对 CMP-Leg5Ac7Ac 有显著的活性，与 CMP-Neu5Ac 相比，活性提高了 60%。光杆菌 α2,6硅烷基转移酶的活性较弱，相对活性为 6%。然后，Leg5Ac7Ac-α-2,3-乳糖产物作为底物与病毒、细菌和哺乳动物来源的六种硅烷基化酶进行了测试。结果表明，六种病毒、细菌和哺乳动物来源的半乳苷酸酶的活性都远远低于相应的半乳苷酸底物，其中流感病毒 N1 的活性最高，而人类 NEU2 的活性最低。这些结果表明了生产以 Leg5Ac7Ac 残基为末端糖的糖醛酸共轭物的可行性，这种共轭物应具有新的生物特性。

  DOI：

  10.1093/glycob/cwq135
• 作为产物：
  描述：

  尿苷5'-(2-乙酰氨基-2-脱氧-ALPHA-D-葡糖基焦磷酸酯) 在 L-谷氨酸 、 磷酸吡哆醛 、 PglE enzyme from Campylobacter jejuni 、 PglF cloned enzyme from Campylobacter jejuni 作用下， 以 aq. buffer 为溶剂， 以65%的产率得到UDP-4-amino sugar
  参考文献：
  名称：

  辅因子驱动的级联反应使糖核苷酸的高效制备成为可能

  摘要：

  糖核苷酸的复杂从头生物合成被重组为级联反应。通过添加辅因子再生系统提供的过量辅因子，将级联反应驱动到目标糖核苷酸的形成，从而产生高合成产量。

  DOI：

  10.1002/anie.202115696

文献信息

• Biochemical Characterization of the O-Linked Glycosylation Pathway in <i>Neisseria gonorrhoeae</i> Responsible for Biosynthesis of Protein Glycans Containing <i>N</i>,<i>N</i>′-Diacetylbacillosamine
  作者：Meredith D. Hartley、Michael J. Morrison、Finn Erik Aas、Bente Børud、Michael Koomey、Barbara Imperiali

  DOI：10.1021/bi2003372

  日期：2011.6.7

  The O-linked protein glycosylation pathway in Neisseria gonorrhoeae is responsible for the synthesis of a complex oligosaccharide on undecaprenyl diphosphate and subsequent en bloc transfer of the glycan to serine residues of select periplasmic proteins. Protein glycosylation (pgl) genes have been annotated on the basis of bioinformatics and top-down mass spectrometry analysis of protein modifications in pgl-null strains [Aas, F. E., et al. (2007) Mol. Microbiol. 65, 607-624; Vik, A., et al. (2009) Proc. Natl. Acad. Sci. U.S.A. 106, 4447-4452], but relatively little biochemical analysis has been performed to date. In this report, we present the expression, purification, and functional characterization of seven Pgl enzymes. Specifically, the enzymes studied are responsible for synthesis of an uncommon uridine diphosphate (UDP)-sugar (PglD, PglC, and PglB-acetyltransferase domain), glycan assembly (PglB-phospho-glycosyltransferase domain, PglA, PglE, and PglH), and final oligosaccharide transfer (PglO). UDP-2,4-diacetamido-2,4,6-trideoxy-alpha-D-hexose (DATDH), which is the first sugar in glycan biosynthesis, was produced enzymatically, and the stereochemistry was assigned as uridine diphosphate N'-diacetylbacillosamine (UDP-diNAcBac) by nuclear magnetic resonance characterization. In addition, the substrate specificities of the phospho-glycosyltransferase, glycosyltransferases, and oligosaccharyltransferase (OTase) were analyzed in vitro, and in most cases, these enzymes exhibited strong preferences for the native substrates relative to closely related glycans. In particular, PglO, the O-linked OTase, and PglB(Cj), the N-linked OTase from Campylobacter jejuni, preferred the native N. gonorrhoeae and C. jejuni substrates, respectively. This study represents the first comprehensive biochemical characterization of this important 0-linked glycosylation pathway and provides the basis for further investigations of these enzymes as antibacterial targets.
• Enzymatic synthesis and properties of glycoconjugates with legionaminic acid as a replacement for neuraminic acid
  作者：D. C. Watson、S. Leclerc、W. W. Wakarchuk、N. M. Young

  DOI：10.1093/glycob/cwq135

  日期：2011.1.1

  In addition to sialic acid, bacteria produce several other nonulosonic acids, including legionaminic acid (Leg). This has exactly the same stereochemistry as sialic acid, with the added features of 9-deoxy and 7-amino groups. In order to explore the biological effects of replacing sialic acid residues (Neu5Ac) in glycoconjugates with Leg in its diacetylated form, diacetyllegionaminic acid (Leg5Ac7Ac), we tested CMP-Leg5Ac7Ac as a donor substrate with a selection of bacterial and mammalian sialyltransferases. The CMP-Leg5Ac7Ac was synthesized in vitro by means of cloned enzymes from the bacillosamine portion of the Campylobacter jejuni N-glycan pathway and from the Leg pathway of Legionella pneumophila. Using fluorescent derivatives of lactose, Galβ1,4GlcNAcβ and T-antigen (Galβ1,3GalNAcα) as acceptors, we tested eight different sialyltransferases and found that the Pasteurella multocida PM0188h and porcine ST3Gal1 sialyltransferases were significantly active with CMP-Leg5Ac7Ac, showing ∼60% activity when compared with CMP-Neu5Ac. The Photobacterium α2,6 sialyltransferase was weakly active, with ∼6% relative activity. The Leg5Ac7Ac-α-2,3-lactose product was then tested as a substrate with six sialidases of viral, bacterial and mammalian origin. All showed much lower activities than with the corresponding sialic acid substrate, with the influenza virus N1 being the most active and human NEU2 being the least active. These results show the feasibility of producing glycoconjugates with Leg5Ac7Ac residues as the terminal sugars, which should display novel biological properties.

  除硅醛酸外，细菌还产生其他几种非乌洛托品酸，包括军团酰胺酸（Leg）。这种酸的立体化学结构与硅藻酸完全相同，但增加了 9-脱氧基团和 7-氨基基团。为了探索用 Leg 的双乙酰化形式--双乙酰军团胺酸（Leg5Ac7Ac）--取代糖醛酸残基（Neu5Ac）对生物的影响，我们用细菌和哺乳动物的部分硅烷基转移酶测试了 CMP-Leg5Ac7Ac 作为供体底物的效果。CMP-Leg5Ac7Ac 是通过克隆空肠弯曲杆菌 N-聚糖途径中的巴基氨基部分和嗜肺军团菌途径中的酶在体外合成的。我们使用乳糖的荧光衍生物、Galβ1,4GlcNAcβ和T-抗原（Galβ1,3GalNAcα）作为受体，测试了八种不同的硅烷基转移酶，发现多杀性巴氏杆菌 PM0188h 和猪 ST3Gal1 硅烷基转移酶对 CMP-Leg5Ac7Ac 有显著的活性，与 CMP-Neu5Ac 相比，活性提高了 60%。光杆菌 α2,6硅烷基转移酶的活性较弱，相对活性为 6%。然后，Leg5Ac7Ac-α-2,3-乳糖产物作为底物与病毒、细菌和哺乳动物来源的六种硅烷基化酶进行了测试。结果表明，六种病毒、细菌和哺乳动物来源的半乳苷酸酶的活性都远远低于相应的半乳苷酸底物，其中流感病毒 N1 的活性最高，而人类 NEU2 的活性最低。这些结果表明了生产以 Leg5Ac7Ac 残基为末端糖的糖醛酸共轭物的可行性，这种共轭物应具有新的生物特性。
• Cofactor‐Driven Cascade Reactions Enable the Efficient Preparation of Sugar Nucleotides
  作者：Yuan Zheng、Jiabin Zhang、Jeffrey Meisner、Wanjin Li、Yawen Luo、Fangyu Wei、Liuqing Wen

  DOI：10.1002/anie.202115696

  日期：2022.5.9

  The complex de novo biosynthesis of sugar nucleotides was reorganized as cascade reactions. The cascade reactions were driven toward the formation of the target sugar nucleotides through the addition of an excess amount of a cofactor provided by a cofactor regeneration system, thus resulting in high synthetic yields.

  糖核苷酸的复杂从头生物合成被重组为级联反应。通过添加辅因子再生系统提供的过量辅因子，将级联反应驱动到目标糖核苷酸的形成，从而产生高合成产量。