P'-[2-(acetylamino)-2-deoxy-α-D-glucopyranosyl] ester uridine 5'-(trihydrogen diphosphate), disodium salt | 91183-98-1

• 物质功能分类: 生物化工 - 糖类化合物 - 单糖
• 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: P'-[2-(acetylamino)-2-deoxy-α-D-glucopyranosyl] ester uridine 5'-(trihydrogen diphosphate), disodium salt
• 英文别名: uridine 5'-(2-acetamido-2-deoxy-α-D-glucopyranosyl diphosphate) disodium salt；2-acetamido-2-deoxy-α-D-glucosyl uridine diphosphate disodium salt；uridine 5'-diphosphate-N-acetylglucosamine disodium salt；UDP-N-acetyl-α-D-glucosamine disodium salt；UDP-α-D-N-acetylglucosamine disodium salt；UDP-N-acetylglucosamine disodium salt
• CAS: 91183-98-1
• 化学式: C₁₇H₂₅N₃O₁₇P₂*2Na
• 分子量: 651.322
• InChiKey: ZRSWQYRIHMWMEJ-ACWDWNMJSA-L

物化性质

• 溶解度：
  可溶于甲醇（轻微加热）、水（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  -8.91
• 重原子数：
  40.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  311.52
• 氢给体数：
  7.0
• 氢受体数：
  18.0

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• 安全说明：
  S22,S26,S36
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

制备方法与用途

生物活性

UDP-GlcNAc Disodium Salt (UDP-α-D-N-Acetylglucosamine Disodium Salt) 是 O-GlcNAc 转移酶 (OGT) 的供体底物。

体外研究

OGT is a nucleocytoplasmic glycosyltransferase (uridine diphospho-N--acetylglucosamine:polypeptide β-N-acetylglucosaminyltransferase or O-GlcNAc transferase) assigned to the GT41 family in the CAZY (Carbohydrate-Active enZYme) database. Using UDP-GlcNAc Disodium Salt (UDP-GlcNAc) as the donor substrate, this enzyme modifies thousands of proteins by adding a unique N-acetylglucosamine residue onto acceptor substrates mainly confined within cytosol and nucleus.

反应信息

• 作为反应物：
  描述：

  P'-[2-(acetylamino)-2-deoxy-α-D-glucopyranosyl] ester uridine 5'-(trihydrogen diphosphate), disodium salt 在 pyruvate kinase 、 3,3,3-膦三基三丙酸 、 磷烯醇丙酮酸 、 还原型辅酶Ⅰ 、 magnesium chloride 、 L-lactate dehydrogenase 作用下， 以 aq. buffer 为溶剂， 反应 0.17h， 生成 尿苷-5’-二磷酸
  参考文献：
  名称：

  The Glycosyltransferase Involved in Thurandacin Biosynthesis Catalyzes Both O- and S-Glycosylation

  摘要：

  The S-glycosyltransferase SunS is a recently discovered enzyme that selectively catalyzes the conjugation of carbohydrates to the cysteine thiol of proteins. This study reports the discovery of a second S-glycosyltransferase, ThuS, and shows that ThuS catalyzes both S-glycosylation of the thiol of cysteine and O-glycosylation of the hydroxyl group of serine in peptide substrates. ThuS-catalyzed S-glycosylation is more efficient than O-glycosylation, and the enzyme demonstrates high tolerance with respect to both nucleotide sugars and peptide substrates. The biosynthesis of the putative products of the thuS gene cluster was reconstituted in vitro, and the resulting S-glycosylated peptides thurandacin A and B exhibit highly selective antimicrobial activity toward Bacillus thuringiensis.

  DOI：

  10.1021/ja411159k
• 作为产物：
  描述：

  2-叠氮基-2-脱氧-D-吡喃葡萄糖1,3,4,6-四乙酸酯 在 1,4-dithio-D,L-threitol 、 磷酸 、 氢气 、 sodium methylate 、 magnesium chloride 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 P'-[2-(acetylamino)-2-deoxy-α-D-glucopyranosyl] ester uridine 5'-(trihydrogen diphosphate), disodium salt
  参考文献：
  名称：

  Chemoenzymatic Synthesis of Uridine Diphosphate-GlcNAc and Uridine Diphosphate-GalNAc Analogs for the Preparation of Unnatural Glycosaminoglycans

  摘要：

  Eight N-acetylglucosamine-1-phosphate and N-acetylgalactosamine-1-phosphate analogs have been synthesized chemically and were tested for their recognition by the GlmU uridyltransferase enzyme. Among these, only substrates that have an amide linkage to the C-2 nitrogen were transferred by GlmU to afford their corresponding uridine diphosphate(UDP)-sugar nucleotides. Resin-immobilized GlmU showed comparable activity to nonimmobilized GlmU and provides a more facile final step in the synthesis of an unnatural UDP-donor. The synthesized unnatural UDP-donors were tested for their activity as substrates for glycosyltransferases in the preparation of unnatural glycosaminoglycans in vitro. A subset of these analogs was useful as donors, increasing the synthetic repertoire for these medically important polysaccharides.

  DOI：

  10.1021/jo202322k
• 作为试剂：
  描述：

  N-MeDCPA 在 乙二胺四乙酸 、 谷胱甘肽 、 uridine 5'-diphosphoglucuronic acid triammonium salt 、 P'-[2-(acetylamino)-2-deoxy-α-D-glucopyranosyl] ester uridine 5'-(trihydrogen diphosphate), disodium salt 、 6-氨基-9-[3-羟基-5-[(羟基-磺基氧基-磷酰)氧基甲基]-4-膦酰氧基-四氢呋喃-2-基]-嘌呤 、 还原型辅酶II(NADPH)四钠盐 、 还原型辅酶Ⅰ 、 magnesium chloride 、 1,4-二巯基-2,3-丁二醇 作用下， 以 aq. phosphate buffer 为溶剂， 生成 3,4-二氯-N-甲基苯胺 、
  参考文献：
  名称：

  Preclinical evaluation of ELP‐004 in mice

  摘要：

  This study provides a detailed understanding of the preclinical pharmacokinetics and metabolism of ELP‐004, an osteoclast inhibitor in development for the treatment of bone erosion. Current treatments for arthritis, including biological disease‐modifying antirheumatic drugs, are not well‐tolerated in a substantial subset of arthritis patients and are expensive; therefore, new treatments are needed. Pharmacokinetic parameters of ELP‐004 were tested with intravenous, oral, and subcutaneous administration and found to be rapidly absorbed and distributed. We found that ELP‐004 was non‐mutagenic, did not induce chromosome aberrations, non‐cardiotoxic, and had minimal off‐target effects. Using in vitro hepatic systems, we found that ELP‐004 is primarily metabolized by CYP1A2 and CYP2B6 and predicted metabolic pathways were identified. Finally, we show that ELP‐004 inhibits osteoclast differentiation without suppressing overall T‐cell function. These preclinical data will inform future development of an oral compound as well as in vivo efficacy studies in mice.

  DOI：

  10.1002/prp2.1230

文献信息

• A Novel Linker Methodology for the Synthesis of Tailored Conjugate Vaccines Composed of Complex Carbohydrate Antigens and Specific T_H‐Cell Peptide Epitopes
  作者：Sebastian Dziadek、Sandra Jacques、David R. Bundle

  DOI：10.1002/chem.200800065

  日期：2008.6.27

  protein (hsp60). Moreover, the linkage chemistry has proven well suited for the synthesis of more complex target structures such as a biotinylated glycopeptide, a three component vaccine containing an immunostimulatory peptide epitope from interleukin-1 beta (IL-1 beta), and for the conjugation of complex carbohydrates to carrier proteins such as bovine serum albumin.

  致病生物或致癌转化细胞通常在其细胞表面表达复杂的碳水化合物结构，这是主动免疫疗法的可行目标。我们在这里描述了一种新型的，免疫中性的，用于高效制备结合复杂糖抗原与特定TH细胞肽表位的高清晰度疫苗偶联物的方法。这种新颖的异双功能方法被用于从致病性真菌白色念珠菌中将（1-> 2）-β-甘露聚糖三糖以及肿瘤相关神经节苷脂GM2的碳水化合物部分与TH细胞肽表位偶联鼠60 kDa自热休克蛋白（hsp60）。此外，事实证明，连接化学非常适合合成更复杂的目标结构，例如生物素化糖肽，
• Chemo-enzymatic synthesis of trimeric sialyl Lewis^xpentadecasaccharide
  作者：Yeuk Chuen Liu、Hong Li、Albin Otter、Vivekanand P Kamath、Markus B Streiff、Monica M Palcic

  DOI：10.1139/v02-073

  日期：2002.6.1

  The enzymatic synthesis of trimeric sialyl Lewis^xpentadecasaccharide (6), a 15-mer, from a trimannoside precursor required six different glycosyltransferase enzymes and four nucleotide donor sugars. Three N-acetylglucosaminyl residues were transferred from UDP-N-acetylglucosamine to a trimannoside by N-acetylglucosaminyltransferases I, II, and V, respectively. Galactosylation using β(1[Formula: see text]4) galactosyltransferase and UDP-galactose gave three N-acetyl lactosamine units in nonasaccharide 4. Sialylation of 4 with α(2[Formula: see text]3) sialyltransferase and CMP-N-acetylneuraminic acid was followed by fucosylation with α(1[Formula: see text]3) fucosyltransferase and GDP-fucose giving the 15-mer 6 in mg quantities. Compound 4 was also converted to a trimeric Lewis^xdodecasaccharide 12-mer with α(1[Formula: see text]3) fucosyltransferase and GDP-fucose and to a trimeric α-2,6-sialyl N-acetyllactosamine dodecasaccharide 12-mer with α(2[Formula: see text]6) sialyltransferase and CMP-N-acetylneuraminic acid. Key words: glycosyltransferases, pentadecasaccharide, sialyl Lewis^x.

  三糖苷前体通过六种不同的糖基转移酶和四种核苷酸供糖进行酶促合成，生成三聚体唾液酸化路易斯^x十五糖（6）。三个N-乙酰葡萄糖胺残基分别通过N-乙酰葡萄糖胺转移酶I、II和V从UDP-N-乙酰葡萄糖胺转移到一个三糖苷上。使用β(1[Formula: see text]4)半乳糖基转移酶和UDP-半乳糖进行半乳糖基化，在九糖4中形成三个N-乙酰乳糖胺单位。4与α(2[Formula: see text]3)唾液酸转移酶和CMP-N-乙酰神经氨酸进行唾液酸化，然后通过α(1[Formula: see text]3)岩藻糖基转移酶和GDP-岩藻糖进行岩藻糖基化，生成毫克级的十五糖6。化合物4还通过α(1[Formula: see text]3)岩藻糖基转移酶和GDP-岩藻糖转化为三聚体路易斯^x十二糖12-mer，以及通过α(2[Formula: see text]6)唾液酸转移酶和CMP-N-乙酰神经氨酸转化为三聚体α-2,6-唾液酸化N-乙酰乳糖胺十二糖12-mer。关键词：糖基转移酶，十五糖，唾液酸化路易斯^x。

• Combined chemical-enzymic synthesis of deoxygenated oligosaccharide analogs: transfer of deoxygenated d-GlcpNAc residues from their UDP-GlcpNAc derivatives using N-acetylglucosaminyltransferase I
  作者：Geeta Srivastava、Gordon Alton、Ole Hindsgaul

  DOI：10.1016/0008-6215(90)84053-w

  日期：1990.10

  hydrogen. The tetrasaccharide glycosides 6 and 12-14 were characterized by 1H-n.m.r. spectroscopy and evaluated as acceptors for GnT-II, the next enzyme in the pathway of biosynthesis of Asn-linked oligosaccharides. Deoxygenation of the 3-position of the beta-D-GlcNAc residue of 6 completely abolished its acceptor activity, whereas removal of HO-4 or HO-6 caused only modest decreases in activity.

  UDP-GlcpNAc的3''-，4''-和6''-脱氧类似物已化学合成，并被发现可作为人乳中N-乙酰氨基葡萄糖基转移酶-I（GnT-1）的供体底物。在存在alpha-D-Manp-（1 ---- 3）-[alpha-D-Manp-（1 ---- 6）]-beta的情况下将UDP-GlcpNAc和这些脱氧类似物与GnT-1一起孵育-D-Manp -O（CH2）8COOMe得到了beta-D-GlcpNAc-（1 ---- 2）-alpha-D-Manp-（1 ---- 3）-[alpha-D-Manp-（1 ---- 6）]-beta-D-Manp-O（ ）8COOMe（6），和脱氧类似物12-14，其中beta-D-Manp-O（ ）8COOMe分别为HO-3，HO-4和HO-6 D-GlcNAc残基被氢取代。通过1H-nmr光谱对四糖苷6和12-14进行了表征，并被评估为GnT
• Enzymatic Synthesis of 2-(β-Galactosyl)-ethyl Methacrylate by β-Galactosidase from <i>Pyrococcus woesei</i> and Application for Glycopolymer Synthesis and Lectin Studies
  作者：Marius Hoffmann、Elisabeth Gau、Susanne Braun、Andrij Pich、Lothar Elling

  DOI：10.1021/acs.biomac.9b01647

  日期：2020.2.10

  for the synthesis of glycosides by transglycosylation reactions. Especially glycosidases from hyperthermophilic bacteria are useful for reactions under extreme reaction conditions, e.g., in the presence of organic solvents. We herein report the facile enzymatic synthesis and purification of 2-(β-galactosyl)-ethyl methacrylate (Gal-EMA) with the recombinant hyperthermostable glycosidase from Pyrococcus

  糖苷酶长期以来一直用于通过转糖基化反应合成糖苷。特别是来自嗜热细菌的糖苷酶可用于极端反应条件下的反应，例如在有机溶剂的存在下。我们在此报道了以高产率从重组火球菌得到的2-（β-半乳糖基）-甲基丙烯酸乙酯（Gal-EMA）的简便酶促合成和纯化。优化的反应条件导致了半乳糖基化单体的克级合成，转糖基化率为88％。Gal-EMA产物的特征在于高效液相色谱-电喷雾电离质谱（HPLC-ESI-MS），核磁共振（NMR）光谱和红外（IR）光谱。Gal-EMA用于合成糖官能化的丙烯酸酯聚合物，其中掺入了一定量的半乳糖（0-100％）。使用酶联凝集素测定（ELLA）分析来自蓖麻的凝集素RCA120与糖聚合物的结合亲和力，发现KD值介于0.24和6.2 nM之间，具体取决于掺入的Gal-EMA的量。Gal-EMA合成丙烯酸酯官能化的聚糖低聚物的潜力已通过两个糖基转移酶顺序延长末端半乳糖而得到证实，从而产生了末
• Construction and Structural Characterization of Versatile Lactosaminoglycan-Related Compound Library for the Synthesis of Complex Glycopeptides and Glycosphingolipids
  作者：Kentarou Naruchi、Tomoki Hamamoto、Masaki Kurogochi、Hiroshi Hinou、Hiroki Shimizu、Takahiko Matsushita、Naoki Fujitani、Hirosato Kondo、Shin-Ichiro Nishimura

  DOI：10.1021/jo0617161

  日期：2006.12.1

  We have established a facile and efficient protocol for the preparative-scale synthesis of various compound libraries related to lactosaminoglycans: cell surface oligosaccharides composed of N-acetyllactosamine as a repeating disaccharide unit, based on chemical and enzymatic approaches. Substrate specificity and feasibility of a bacterial glycosyltransferase, Neisseria meningitidis β1,3-N-acetylg

  我们已经建立了一种简便有效的方案，用于制备规模化合成与乳糖胺聚糖有关的各种化合物文库：基于化学和酶促方法，由N-乙酰基乳糖胺作为重复的二糖单元组成的细胞表面寡糖。底物特异性和细菌糖基转移酶的可行性，奈瑟氏脑膜炎β1,3- Ñ -acetylglucosaminyltransferaSE（LgtA），为了合成适合于哺乳动物的构造各种关键中间体进行了调查ö -glycopeptides和鞘糖脂含聚Ñ-乙酰基乳糖胺结构。重组LgtA在强碱性条件（pH = 10，甘氨酸-NaOH缓冲液）和20至30°C的最佳温度范围内表现出最高的糖基转移酶活性。有趣的是，我们发现LgtA判别升丝氨酸和升-苏氨酸和既用作核心-1β1,3- Ñ -acetylglucosaminyltransferaSE和芯2β1,3- Ñ朝向的Fmoc-SER衍生物-acetylglucosaminyltransferaSE，而LgtA显示仅核心2β1