UDP diNAcBac | 877466-29-0

• 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 diNAcBac
• 英文别名: UDP-N,N'-diacetylbacillosamine；[(2R,3R,4S,5S,6R)-3,5-diacetamido-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: 877466-29-0
• 化学式: C₁₉H₃₀N₄O₁₆P₂
• 分子量: 632.412
• InChiKey: KCAODEOZHCZEBC-TUHJILAWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.1
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  289
• 氢给体数：
  8
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  UDP diNAcBac 在 His₆LegG 、 水 、 sodium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 生成 尿苷-5’-二磷酸
  参考文献：
  名称：

  Biosynthesis of CMP-legionaminic acid from fructose-6-P

  摘要：

  公开号：

  EP2379735B1
• 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 、 Campylobacter jejuni hexa-His-tagged PglD acetyltransferase 、 Campylobacter jejuni hexa-His-tagged PglE aminotransferase 、 Campylobacter jejuni hexa-His-tagged PglF dehydratase 、 磷酸吡哆醛 作用下， 反应 17.0h， 生成 UDP diNAcBac
  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

文献信息

• 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。
• Chemoenzymatic synthesis of an isoprenoid phosphate tool for the analysis of complex bacterial oligosaccharide biosynthesis
  作者：Donovan K. Lujan、Jennifer A. Stanziale、Anahita Z. Mostafavi、Sunita Sharma、Jerry M. Troutman

  DOI：10.1016/j.carres.2012.06.014

  日期：2012.10

  Undecaprenyl Pyrophosphate Synthase (UPPS) is a key enzyme that catalyzes the production of bactoprenols, which act as membrane anchors for the assembly of complex bacterial oligosaccharides. One of the major hurdles in understanding the assembly of oligosaccharide assembly is a lack of chemical tools to study this process, since bactoprenols and the resulting isoprenoid-linked oligosaccharides lack handles or chromophores for use in pathway analysis. Here we describe the isolation of a new UPPS from the symbiotic microorganism Bacteroides fragilis, a key species in the human microbiome. The protein was purified to homogeneity and utilized to accept a chromophore containing farnesyl diphosphate analogue as a substrate. The analogue was utilized by the enzyme and resulted in a bactoprenyl diphosphate product with an easy to monitor tag associated with it. Furthermore, the diphosphate is shown to be readily converted to monophosphate using a common molecular biology reagent. This monophosphate product allowed for the investigation of complex oligosaccharide biosynthesis, and was used to probe the activity of glycosyltransferases involved in the well characterized Campylobacter jejuni N-linked protein glycosylation. Novel reagents similar to this will provide key tools for the study of uncharacterized oligosaccharide assemblies, and open the possibility for the development of rapid screening methodology for these biosynthetic systems. (c) 2012 Elsevier Ltd. All rights reserved.
• Chemoenzymatic synthesis of polyprenyl phosphates
  作者：Meredith D. Hartley、Angelyn Larkin、Barbara Imperiali

  DOI：10.1016/j.bmc.2008.03.025

  日期：2008.5

  Polyprenyl phosphates, including undecaprenyl phosphate and dolichyl phosphate, are essential intermediates in several important biochemical pathways including N-linked protein glycosylation in eukaryotes and prokaryotes and prokaryotic cell wall biosynthesis. Herein, we describe the evaluation of three potential undecaprenol kinases as agents for the chemoenzymatic synthesis of polyprenyl phosphates. Target enzymes were expressed in crude cell envelope fractions and quantified via the use of luminescent lanthanide-binding tags (LBTs). The Streptococcus mutans diacylglycerol kinase (DGK) was shown to be a very useful agent for polyprenol phosphorylation using ATP as the phosphoryl transfer agent. In addition, the S. mutans DGK can be coupled with two Campylobacter jejuni glycosyltransferases involved in N-linked glycosylation to efficiently biosynthesize the undecaprenyl pyrophosphate-linked disaccharide needed for studies of PglB, the C. jejuni oligosaccharyl transferase. (C) 2008 Elsevier Ltd. All rights reserved.
• Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling
  作者：Vinita Lukose、Garrett Whitworth、Ziqiang Guan、Barbara Imperiali

  DOI：10.1021/jacs.5b07146

  日期：2015.10.7

  The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions.
• 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.