2'-azidoethyl β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1->3)-β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranoside | 904925-99-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2'-azidoethyl β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1->3)-β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranoside
• 英文别名: 2-azidoethyl(β-D-galactopyranosyl)-(1→4)-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→3)-(β-D-galactopyranosyl)-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranoside；N-[(2R,3R,4R,5S,6R)-5-[(2S,3R,4S,5S,6R)-4-[(2S,3R,4R,5S,6R)-3-acetamido-4-hydroxy-6-(hydroxymethyl)-5-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-(2-azidoethoxy)-4-hydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide
• CAS: 904925-99-1
• 化学式: C₃₀H₅₁N₅O₂₁
• 分子量: 817.756
• InChiKey: UAOPXLXZQZODTM-QLUZKDHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7
• 重原子数：
  56
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  369
• 氢给体数：
  13
• 氢受体数：
  23

反应信息

• 作为反应物：
  描述：

  2'-azidoethyl β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1->3)-β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranoside 、 cytidine-5'-monophosphono-N-acetylneuraminic acid 在 ST₃Gal-CMP-Neup₅Ac fusion protein 、 sodium cacodylate 、 manganese(ll) chloride 作用下， 以 水 为溶剂， 反应 18.0h， 以86%的产率得到2'-azidoethyl 5-N-acetyl-α-neuraminyl-(2->3)-β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1->3)-β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  Large-scale chemoenzymatic synthesis of blood group and tumor-associated poly-N-acetyllactosamine antigens

  摘要：

  Poly-N-acetyllactosamines (pLNs) are common terminal sugars of many N- and O-linked glycan structures present in glycoproteins and glycolipids. Utilizing various glycosyltransferases, we developed new and efficient chemoenzymatic methods for the synthesis of pLNs in gram-scale. Specifically, the use of sialyltransferases and fucosyltransferases enabled us to synthesize and purify 24 blood group and tumor-associated pLN derivatives with alpha-(2 -> 3)- and alpha-(2 -> 6)-linked sialic acid, as well as with alpha-(1 -> 2)- and alpha-(1 -> 3)-linked fucose. All synthesized derivatives were linked to a short 2-azidoethyl spacer for further modification. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2006.03.043
• 作为产物：
  描述：

  2-azidoethyl(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-(1→4)-(3,6-di-O-acetyl-2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→3)-(2,4,6-tri-O-acetyl-β-D-galactopyranosyl)-(1→4)-3,6-di-O-acetyl-2-acetamido-2-deoxy-β-D-glucopyranoside 在 sodium methylate 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 以94%的产率得到2'-azidoethyl β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1->3)-β-D-galactopyranosyl-(1->4)-2-acetamido-2-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  Galectin-聚糖相互作用：通过77Se NMR光谱和溶剂（H2O / D2O）对结合的影响进行监测的指南。

  摘要：

  细胞糖缀合物和组织凝集素（如半乳凝素）之间的功能配对具有广泛的（病理）生理学意义。天然O-糖苷的不可水解衍生物（例如S-和Se-糖苷）促进了他们的研究。后者可以通过特定的77 Se NMR光谱进行广泛的分析，但仍未得到充分开发。通过使用硒二半乳糖苷（SeDG）和人半乳糖凝集素-1和-3的实例，我们评估了多种77 Se NMR检测方法，并提出了选择性1 H，77Se异核Hartmann-Hahn转移可有效用于针对硒代糖苷间谍配体的竞争NMR筛选。通过荧光各向异性，圆二色性和等温滴定热法（ITC），我们显示了半乳糖凝集素结合SeDG的亲和力和热力学类似于硫代双糖苷（TDG）和N-乙酰基乳糖胺（LacNAc），证实了Se取代没有主要影响。对于DDG和LacNAc的两种半乳糖凝集素结合，D 2 O与H 2 O中的ITC数据相似，但是对于SeDG暗示了溶剂作用，表明溶剂在结合位点的重排，对于具有延长链长的LacNAc二聚体清楚地观察到。

  DOI：

  10.1002/chem.202003143

文献信息

• Synthesis of Biologically Active <i>N</i>- and <i>O</i>-Linked Glycans with Multisialylated Poly-<i>N</i>-acetyllactosamine Extensions Using <i>P. damsela</i> α2-6 Sialyltransferase
  作者：Corwin M. Nycholat、Wenjie Peng、Ryan McBride、Aristotelis Antonopoulos、Robert P. de Vries、Zinaida Polonskaya、M.G. Finn、Anne Dell、Stuart M. Haslam、James C. Paulson

  DOI：10.1021/ja409781c

  日期：2013.12.11

  synthesis of a library of N- and O-linked glycans with multisialylated poly-LacNAc extensions, including naturally occurring multisialylated core-3 O-linked glycans. We have found that a recombinant α2-6 sialyltransferase from Photobacterium damsela (Pd2,6ST) exhibits unique regioselectivity and is able to sialylate internal galactose residues in poly-LacNAc extended glycans which was confirmed by MS/MS

  N 和 O 连接糖蛋白上的唾液酸苷在许多生物过程中发挥着重要作用，合成聚糖探针已被证明是阐明这些功能的有价值的工具。虽然唾液酸通常以 α2-3- 或 α2-6- 连接到末端非还原端半乳糖，但据报道，从大鼠唾液腺和人结肠粘蛋白中分离出来的 poly-LacNAc 延伸的 core-3 O-连接聚糖含有多种内部Neu5Acα2-6Gal 表位。在这里，我们开发了一种有效的方法来合成具有多唾液酸化 poly-LacNAc 扩展的 N-和 O-连接聚糖库，包括天然存在的多唾液酸化 core-3 O-连接聚糖。我们发现来自 Photobacterium damsela (Pd2, 6ST) 具有独特的区域选择性，并且能够唾液酸化 poly-LacNAc 延伸聚糖中的内部半乳糖残基，这已通过 MS/MS 分析得到证实。使用显示该库的聚糖微阵列，我们发现 Neu5Acα2-6Gal 特异性流感病毒血凝素、siglecs
• CD22 Ligands on a Natural <i>N</i>-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells
  作者：Wenjie Peng、James C. Paulson

  DOI：10.1021/jacs.7b03208

  日期：2017.9.13

  CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. Binding affinity is increased by up to 1500-fold compared to the monovalent ligand, while maintaining the selectivity for hCD22 over other Siglecs. Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs.
• Large-scale chemoenzymatic synthesis of blood group and tumor-associated poly-N-acetyllactosamine antigens
  作者：Daniela Vasiliu、Nahid Razi、Yingning Zhang、Nathan Jacobsen、Kirk Allin、Xiaofei Liu、Julia Hoffmann、Ognian Bohorov、Ola Blixt

  DOI：10.1016/j.carres.2006.03.043

  日期：2006.7

  Poly-N-acetyllactosamines (pLNs) are common terminal sugars of many N- and O-linked glycan structures present in glycoproteins and glycolipids. Utilizing various glycosyltransferases, we developed new and efficient chemoenzymatic methods for the synthesis of pLNs in gram-scale. Specifically, the use of sialyltransferases and fucosyltransferases enabled us to synthesize and purify 24 blood group and tumor-associated pLN derivatives with alpha-(2 -> 3)- and alpha-(2 -> 6)-linked sialic acid, as well as with alpha-(1 -> 2)- and alpha-(1 -> 3)-linked fucose. All synthesized derivatives were linked to a short 2-azidoethyl spacer for further modification. (c) 2006 Elsevier Ltd. All rights reserved.
• Galectin–Glycan Interactions: Guidelines for Monitoring by⁷⁷Se NMR Spectroscopy, and Solvent (H₂O/D₂O) Impact on Binding
  作者：Tammo Diercks、Francisco J. Medrano、Forrest G. FitzGerald、Donella Beckwith、Martin Jaeger Pedersen、Mark Reihill、Anna‐Kristin Ludwig、Antonio Romero、Stefan Oscarson、Maré Cudic、Hans‐Joachim Gabius

  DOI：10.1002/chem.202003143

  日期：2021.1.4

  diverse 77Se NMR detection methods and propose selective 1H,77Se heteronuclear Hartmann–Hahn transfer for efficient use in competitive NMR screening against a selenoglycoside spy ligand. By fluorescence anisotropy, circular dichroism, and isothermal titration calorimetry (ITC), we show that the affinity and thermodynamics of SeDG binding by galectins are similar to thiodigalactoside (TDG) and N‐acetyllactosamine

  细胞糖缀合物和组织凝集素（如半乳凝素）之间的功能配对具有广泛的（病理）生理学意义。天然O-糖苷的不可水解衍生物（例如S-和Se-糖苷）促进了他们的研究。后者可以通过特定的77 Se NMR光谱进行广泛的分析，但仍未得到充分开发。通过使用硒二半乳糖苷（SeDG）和人半乳糖凝集素-1和-3的实例，我们评估了多种77 Se NMR检测方法，并提出了选择性1 H，77Se异核Hartmann-Hahn转移可有效用于针对硒代糖苷间谍配体的竞争NMR筛选。通过荧光各向异性，圆二色性和等温滴定热法（ITC），我们显示了半乳糖凝集素结合SeDG的亲和力和热力学类似于硫代双糖苷（TDG）和N-乙酰基乳糖胺（LacNAc），证实了Se取代没有主要影响。对于DDG和LacNAc的两种半乳糖凝集素结合，D 2 O与H 2 O中的ITC数据相似，但是对于SeDG暗示了溶剂作用，表明溶剂在结合位点的重排，对于具有延长链长的LacNAc二聚体清楚地观察到。