O-[(α-D-mannopyranosyl)-(1->6)-(α-D-mannopyranosyl)-(1->3)-β-D-mannopyranosyl]-(1->4)-(1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-methyloxazoline | 861695-58-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: O-[(α-D-mannopyranosyl)-(1->6)-(α-D-mannopyranosyl)-(1->3)-β-D-mannopyranosyl]-(1->4)-(1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-methyloxazoline
• 英文别名: 2-methyl-[α-D-mannopyranosyl-(1→3)-[α-D-mannopyranosyl-(1→6)]-β-D-glucopyranosyl-(1→4)-α-D-glucopyrano]-[2,1-d]-oxazoline；Man3-ox；2-methyl-[α-D-mannopyranosyl-(1->3)-[α-D-mannopyranosyl-(1->6)]-β-D-mannopyranosyl-(1->4)-1,2-dideoxy-α-D-glucopyrano]-[2,1-d]oxazoline；2-methyl-[α-D-mannopyranosyl-(1->3)-[α-D-mannopyranosyl-(1->6)]-[β-D-glucopyranosyl-(1->4)]-1,2-dideoxy-α-D-glucopyrano]-[2,1-d]-2-oxazoline；Man3GlcNAc oxazoline；(2S,3S,4S,5S,6R)-2-[[(2R,3R,4S,5S,6S)-6-[[(3aR,5R,6S,7R,7aR)-7-hydroxy-5-(hydroxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]oxazol-6-yl]oxy]-3,5-dihydroxy-4-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
• CAS: 861695-58-1
• 化学式: C₂₆H₄₃NO₂₀
• 分子量: 689.622
• InChiKey: CFJYTGJZCRGCLC-SHYLFXLQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.6
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  329
• 氢给体数：
  12
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  O-[(α-D-mannopyranosyl)-(1->6)-(α-D-mannopyranosyl)-(1->3)-β-D-mannopyranosyl]-(1->4)-(1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-methyloxazoline 、 葛根素 在 endo-β-N-acetylglucosaminidase from Arthrobactor protophormiae 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以60%的产率得到
  参考文献：
  名称：

  Introducing N-glycans into natural products through a chemoenzymatic approach

  摘要：

  The present study describes an efficient chemoenzymatic method for introducing a core N-glycan of glycoprotein origin into various lipophilic natural products. It was found that the endo-beta-N-acetylglucosaminidase from Arthrobactor protophormiae (Endo-A) had broad substrate specificity and can accommodate a wide range of glucose (Glc)- or N-acetylglucosamine (GIcNAc)-containirig natural products as acceptors for transglycosylation, when an N-glycan oxazoline Was used as a donor substrate. Using lithocholic acid as a model compound, we have shown that introduction of an N-glycan could be achieved by a two-step approach: chemical glycosylation to introduce a monosaccharide (GIc or GIcNAc) as a handle, and then Endo-A catalyzed transglycosylation to accomplish the site-specific N-glycan attachment. For those natural products that already carry terminal GIc or GIcNAc residues, direct enzymatic transglycosylation using sugar oxazoline as the donor substrate was achievable to introduce an N-glycan. It was also demonstrated that simultaneous double glycosylation could be fulfilled when the natural product contains two GIc residues. This chemoenzymatic method is concise, site-specific, and highly convergent. Because N-glycans of glycoprotein origin can serve as ligands for diverse lectins and cell-surface receptors, introduction of a defined N-glycan into biologically significant natural products may bestow novel properties onto these natural products for drug discovery and development. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2008.08.033
• 作为产物：
  描述：

  p-methoxyphenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl-(1->3)-[2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl-(1->6)]-2,4-di-O-acetyl-β-D-mannopyranosyl-(1->4)-3,6-di-O-acetyl-2-acetamido-2-deoxy-β-D-glucopyranoside 在 吡啶 、 2,4,6-三甲基吡啶 、 甲醇 、 ammonium cerium (IV) nitrate 、 三甲基溴硅烷 、 三氟化硼乙醚 、 水 、 sodium 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 80.0h， 生成 O-[(α-D-mannopyranosyl)-(1->6)-(α-D-mannopyranosyl)-(1->3)-β-D-mannopyranosyl]-(1->4)-(1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-methyloxazoline
  参考文献：
  名称：

  An Endoglycosidase with Alternative Glycan Specificity Allows Broadened Glycoprotein Remodelling

  摘要：

  Protein endoglycosidases are useful for biocatalytic alteration of glycans on protein surfaces, but the currently limited selectivity of endoglycosidases has prevented effective manipulation of certain N-linked glycans widely found in nature. Here we reveal that a bacterial endoglycosidase from Streptococcus pyogenes, EndoS, is complementary to other known endoglycosidases (EndoA, EndoH) used for current protein remodeling. It allows processing of complex-type N-linked glycans +/- core fucosylation but does not process oligomannose- or hybrid-type glycans. This biocatalytic activity now addresses previously refractory antibody glycoforms.

  DOI：

  10.1021/ja301334b

文献信息

• One-pot N-glycosylation remodeling of IgG with non-natural sialylglycopeptides enables glycosite-specific and dual-payload antibody–drug conjugates
  作者：Feng Tang、Yang Yang、Yubo Tang、Shuai Tang、Liyun Yang、Bingyang Sun、Bofeng Jiang、Jinhua Dong、Hong Liu、Min Huang、Mei-Yu Geng、Wei Huang

  DOI：10.1039/c6ob01751g

  日期：——

  Chemoenzymatic transglycosylation catalyzed by endo-S mutants is a powerful tool for in vitro glycoengineering of therapeutic antibodies. In this paper, we report a one-pot chemoenzymatic synthesis of glycoengineered Herceptin using an egg-yolk sialylglycopeptide (SGP) substrate. Combining this one-pot strategy with novel non-natural SGP derivatives carrying azido or alkyne tags, glycosite-specific

  内切-S突变体催化的化学酶转糖基化是体外的强大工具治疗性抗体的糖工程。在本文中，我们报告了使用蛋黄唾液酸糖肽（SGP）底物进行糖锅赫赛汀的一锅化学酶法合成。通过将这种一锅法与带有叠氮基或炔烃标记的新型非天然SGP衍生物相结合，糖基特异性缀合可以开发新的抗体-药物缀合物（ADC）。通过SDS-PAGE，完整抗体或ADC质谱分析和PNGase-F酶切分析，成功实现了位点特异性ADC和半位点双重药物ADC并进行了表征。癌细胞的细胞毒性测定表明，这些ADC的小分子药物释放依赖于嵌入结构中的可裂解Val-Cit连接片段。
• Specificity of Donor Structures for<i>endo</i>-β-<i>N</i>-Acetylglucosaminidase-Catalyzed Transglycosylation Reactions
  作者：Nozomi Ishii、Ken Ogiwara、Kanae Sano、Jyunichi Kumada、Kenji Yamamoto、Yuji Matsuzaki、Ichiro Matsuo

  DOI：10.1002/cbic.201700506

  日期：2018.1.18

  The sweet spot: The structural specificity of the glycosyl donor for the transglycosylation of endo‐β‐N‐acetylglucosaminidase from M. hiemalis (endo‐M) and its mutants, N175Q and N175A, is investigated by using unnatural tetrasaccharide derivatives. Transglycosylation with donors chemically modified at the C‐4 position of the β‐mannose residue is examined, and transglycosylated products are successfully

  关键点：使用非天然四糖衍生物研究了糖基施主对hi.alis （hiemalis）（endo- M）的内-β- N-乙酰氨基葡糖苷酶及其突变体N175Q和N175A的转糖基化的结构特异性。检查了在β-甘露糖残基C-4位置化学修饰的供体的糖基转移，成功获得了糖基化产物。
• Glycopeptide Synthesis throughendo-Glycosidase-Catalyzed Oligosaccharide Transfer of Sugar Oxazolines: Probing Substrate Structural Requirement
  作者：Ying Zeng、Jingsong Wang、Bing Li、Steven Hauser、Hengguang Li、Lai-Xi Wang

  DOI：10.1002/chem.200501196

  日期：2006.4.12

  An array of sugar oxazolines was synthesized and tested as donor substrates for the Arthrobacter endo-beta-N-acetylglucosaminidase (Endo-A)-catalyzed glycopeptide synthesis. The experiments revealed that the minimum structure of the donor substrate required for Endo-A catalyzed transglycosylation is a Man beta1-->4-GlcNAc oxazoline moiety. Replacement of the beta-D-Man moiety with beta-D-Glc, beta-D-Gal

  合成了一系列糖恶唑啉，并测试了它们作为节杆菌内-β-N-乙酰氨基葡糖苷酶（Endo-A）催化的糖肽合成的供体底物。实验表明，Endo-A催化转糖基化所需的供体底物的最小结构是Man beta1-> 4-GlcNAc恶唑啉部分。用β-D-Glc，β-D-Gal和β-D-GlcNAc单糖替代β-D-Man部分会导致二糖恶唑啉的底物活性降低。尽管如此，该酶仍可耐受修饰，例如在β-D-Man部分的3和/或6位上附加糖残基或官能团的连接，从而使选择性修饰的寡糖成功转移到肽上受体。另一方面，该酶在受体部分具有很大的柔韧性，可以同时使用大大小小的GlcNAc肽作为受体。研究表明，内切糖苷酶催化的转糖基化在构建天然和选择性修饰糖肽方面都具有巨大潜力。
• Endo-β-N-Acetylglucosaminidase catalysed glycosylation: tolerance of enzymes to structural variation of the glycosyl amino acid acceptor
  作者：Yusuke Tomabechi、Marie A. Squire、Antony J. Fairbanks

  DOI：10.1039/c3ob42104j

  日期：——

  Endo-β-N-Acetylglucosaminidases (ENGases) are highly useful biocatalysts that can be used to synthetically access a wide variety of defined homogenous N-linked glycoconjugates in a convergent manner. The synthetic efficiency of a selection of family GH85 ENGases was investigated as the structure of the acceptor substrate was varied. Several different GlcNAc-asparagine acceptors were synthesised, and used in conjunction with penta- and decasaccharide oxazoline donors. Different enzymes showed different tolerances of modification of the GlcNAc acceptor. Whilst none tolerated modification of either the 4- or 6-hydroxyl, both Endo M and Endo D tolerated modification of OH-3. For Endo D the achievable synthetic efficiency was increased by a factor of three by the use a 3-O-benzyl protected acceptor. The presence of a fucose at position-3 was not tolerated by any of the enzymes assayed.

  内转β-N-乙酰氨基葡萄糖苷酶（ENGases）是一类非常有用的生物催化剂，可以以汇聚的方式合成各种定义明确的均相N-连接糖 conjugates。我们研究了几种GH85家族ENGases的合成效率，并改变了受体底物的结构。合成了几种不同的GlcNAc-天冬氨酸受体，并与五糖和十糖的噁唑啉供体结合使用。不同的酶对GlcNAc受体的修改有不同的耐受性。尽管没有一种酶能耐受4-或6-羟基的修饰，但Endo M和Endo D都能耐受OH-3的修饰。对于Endo D，通过使用3-O-苄基保护的受体，提高了可实现的合成效率，增加了三倍。任何被检测的酶都不能耐受在3位的岩藻糖存在。
• Rapid synthesis of N-glycan oxazolines from locust bean gum via the Lafont rearrangement
  作者：Sivasinthujah Paramasivam、Antony J. Fairbanks

  DOI：10.1016/j.carres.2019.03.010

  日期：2019.5

  Enzymatic degradation of locust bean gum provides a Manβ(1 → 4)Man disaccharide, which may be converted into the core Manβ(1 → 4)GlcNAc disaccharide unit of all N-glycans via conversion to a 2-iodo-glycosyl azide, and Lafont rearrangement. The Manβ(1 → 4)GlcNAc disaccharide may be used as a key intermediate for elaboration into more complex N-glycan structures providing a route to N-glycan oxazolines

  刺槐豆胶的酶促降解提供了Manβ（1→4）Man二糖，可通过转化为2-碘-糖基叠氮化物将其转化为所有N-聚糖的核心Manβ（1→4）GlcNAc二糖单元。 Lafont重排。Manβ（1→4）GlcNAc二糖可用作关键中间体，可用于修饰成更复杂的N-聚糖结构，从而提供了一条途径，将N-聚糖恶唑啉作为ENGase酶的供体底物，比以前报道的要短得多。