N^α-fluoren-9-ylmethoxycarbonyl-O-[O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-(1->3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-α-D-galactopyranosyl]-L-threonine | 125760-33-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N^α-fluoren-9-ylmethoxycarbonyl-O-[O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-(1->3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-α-D-galactopyranosyl]-L-threonine
• 英文别名: N^α-fluoren-9-ylmethoxycarbonyl-O-[2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-galactopyranosyl]-L-threonine；N-α-Fmoc-O-[O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-(1→3)]-4,6-di-O-acetyl-2-acetamido-2-deoxy-α-D-galactopyranosyl-L-threonine；Fmoc-(Ac₄Galβ1,3Ac₂GalNAcα1→)Thr；N^α-Fmoc-Thr((AcO)₄Galβ1→3(AcO)₂GalNAcα)-OH；O-[2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-galactopyranosyl]-N-[(9H-fluoren-9-yl)methoxycarbonyl]-L-threonine；N-(9H-fluoren-9-ylmethoxycarbonyl)-O-{2-acetamido-4,6-di-O-acetyl-3-O-[2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl]-2-deoxy-α-D-galactopyranosyl}-L-threonine；Nα-Fmoc-Thr[AcO4Galβ1->3(AcO2GalNAcα)]-OH；Fmoc-Thr(Ac4Galβ1-3Ac2GalNAcα-O-)-OH；(2S,3R)-3-[(2S,3R,4R,5R,6R)-3-Acetamido-5-acetyloxy-6-(acetyloxymethyl)-4-[(2R,3R,4S,5S,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoic acid
• CAS: 125760-33-0
• 化学式: C₄₅H₅₄N₂O₂₁
• 分子量: 958.925
• InChiKey: ZSSXZUSKVRRKAI-UFQULINBSA-N

物化性质

• 沸点：
  996.7±65.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  68
• 可旋转键数：
  25
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  299
• 氢给体数：
  3
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  、 N^α-fluoren-9-ylmethoxycarbonyl-O-[O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-(1->3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-α-D-galactopyranosyl]-L-threonine 在 2,4,6-三甲基吡啶 、 N-羟基-7-氮杂苯并三氮唑 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以73%的产率得到N-α-Fmoc-O-α-(2,3,4,6-tetra-O-acetyl-D-galactopyranosylb-(1-3)-2-acetamido-2-deoxy-3,4,6-tetra-O-acetyl-Dgalactopyranosyl)-L-threonine-(9,12,15,18,21,24,27-heptaoxa-3-thioacetyl-30-azatetratriacontan-33-yl)
  参考文献：
  名称：

  Synthesis and cell-selective antitumor properties of amino acid conjugated tumor-associated carbohydrate antigen-coated gold nanoparticles

  摘要：

  The Thomsen Friedenreich antigen (TFag) disaccharide is a tumor-associated carbohydrate antigen (TACA) found primarily on carcinoma cells and rarely expressed in normal tissue. The TFag has been shown to interact with Galectin-3 (Gal-3), one in a family of beta-galactoside binding proteins. Galectins have a variety of cellular functions, and Gal-3 has been shown to be the sole galectin with anti-apoptotic activity. We have previously prepared gold nanoparticles (AuNP) coated with the TFag in various presentations as potential anti-adhesive therapeutic tools or antitumor vaccine platforms. Here we describe the synthesis of TFag-glycoamino acid conjugates attached to gold nanoparticles through a combined alkane/PEG linker, where the TFag was attached to either a serine or threonine amino acid. Particles were fully characterized by a host of biophysical techniques, and along with a control particle carrying hydroxyl-terminated linker units, were evaluated in both Gal-3 positive and negative cell lines. We show that the particles bearing the saccharides selectively inhibited tumor cell growth of the Gal-3 positive cells significantly more than the Gal-3 negative cells. In addition, the threonine-attached TF particles were more potent than the serine-attached constructs. These results support the use of AuNP as antitumor therapeutic platforms, targeted against cell lines that express specific lectins that interact with TFag. Published by Elsevier Ltd.

  DOI：

  10.1016/j.carres.2014.11.002
• 作为产物：
  描述：

  N-Fmoc-(O-N-acetylgalactosaminyl)threonine tert-butyl ester 在 吡啶 、 4 A molecular sieve 、 氰化汞 、 对甲苯磺酸 、 溶剂黄146 、 三氟乙酸 作用下， 以 硝基甲烷 、 二氯甲烷 、 苯甲醚 、 N,N-二甲基甲酰胺 为溶剂， 25.0~50.0 ℃ 、1.5 kPa 条件下， 生成 N^α-fluoren-9-ylmethoxycarbonyl-O-[O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-(1->3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-α-D-galactopyranosyl]-L-threonine
  参考文献：
  名称：

  Synthetic Glycopeptides of the Tandem Repeat Sequence of the Epithelial Mucin MUC4 with Tumour-associated Carbohydrate Antigens

  摘要：

  通过采用固相方法学，制备了代表上皮粘蛋白MUC4串联重复序列的甘露肽。利用逐步延伸Fmoc保护的半乳糖胺苏氨酸叔丁酯糖侧链的简易仿生策略，合成了包含肿瘤相关糖抗原TN-、T-、唾液酸TN-、(2,6)-和(2,3)-唾液酸T的所需糖基氨基酸构建单元。

  DOI：

  10.1055/s-2003-42029

文献信息

• Synthesis of an Isotopically-labelled Antarctic Fish Antifreeze Glycoprotein Probe
  作者：Joanna M. Wojnar、Clive W. Evans、Arthur L. DeVries、Margaret A. Brimble

  DOI：10.1071/ch10464

  日期：——

  Antifreeze glycoproteins (AFGPs) are glycosylated polypeptides produced by Antarctic and Arctic fishes, which allow them to survive in seawater at sub-zero temperatures. An investigation into the postulated enteric uptake of AFGP synthesized in the exocrine pancreas of Antarctic fishes required a custom-prepared AFGP probe that incorporated seven isotopically-labelled Ala residues for detection by

  抗冻糖蛋白（AFGP）是南极和北极鱼类产生的糖基化多肽，可以使它们在低于零温度的海水中生存。对南极鱼类外分泌胰腺中合成的AFGP的假定肠摄取的调查，需要定制的AFGP探针，该探针结合了7个同位素标记的Ala残基，用于质谱检测。的AFGPs由重复的三个氨基酸单元（丙氨酸-丙氨酸-苏氨酸），其中，所述苏氨酸残基是糖基化与二糖的β- d -Gal-（1→3）-α- d -GalNAc。同位素标记的AFGP8（1）的合成，以及受保护的糖基化氨基酸构件2的优化合成，已报告。
• Synthesis of Tn/T Antigen MUC1 Glycopeptide BSA Conjugates and Their Evaluation as Vaccines
  作者：Hui Cai、Zhi-Hua Huang、Lei Shi、Peng Zou、Yu-Fen Zhao、Horst Kunz、Yan-Mei Li

  DOI：10.1002/ejoc.201100304

  日期：2011.7

  The tumor-associated mucin MUC1 over-expressed in most epithelial tumor tissues is considered a promising target for immunotherapy. The extracellular part of MUC1 contains a domain of numerous tandem repeats of the amino acid sequence HGVTSAPDTRPAPGSTAPPA, including five potential O-glycosylation sites. In this study, T9 and S15 have been chosen as the positions of glycosylation. The glycopeptides N-terminally

  在大多数上皮肿瘤组织中过度表达的肿瘤相关粘蛋白 MUC1 被认为是免疫治疗的有希望的靶点。MUC1 的细胞外部分包含氨基酸序列 HGVTSAPDTRAPPGSTAPPA 的众多串联重复结构域，包括五个潜在的 O-糖基化位点。在本研究中，选择了 T9 和 S15 作为糖基化的位置。通过微波辅助 Fmoc 固相肽合成法合成了 N 端带有三甘醇间隔物的糖肽。从树脂上分离并脱保护后，将 MUC1 糖肽与牛血清白蛋白 (BSA) 结合。为了评估免疫学特性，用这些 BSA 疫苗免疫 balb/c 小鼠。
• Comparing naturally occurring glycosylated forms of proline rich antibacterial peptide, Drosocin
  作者：Deepti S. Lele、Gagandeep Kaur、Menithalaxmi Thiruvikraman、Kanwal J. Kaur

  DOI：10.1007/s10719-017-9781-8

  日期：2017.10

  challenge. We report herein the chemical synthesis of drosocin carrying disaccharide (β-Gal(1 → 3)α-GalNAc) and comparison of its structural and functional properties with another naturally occurring monoglycosylated form of drosocin i.e. α-GalNAc-drosocin as well as with non-glycosylated drosocin. The disaccharide containing drosocin exhibited lower potency compared to monoglycosylated drosocin against

  抗菌肽（AMP）是先天免疫的关键角色。在各种类型的AMPs中，来自昆虫的富含脯氨酸的AMPs受到特别关注，该类中的少数成员带有O-糖基化作为翻译后修饰。果蝇是一种19个氨基酸的糖基化AMP，是富含脯氨酸的成员，在细菌攻击后会在果蝇的血淋巴中合成。我们在这里报告了载有二糖（β-Gal（1→3）α-GalNAc）的drosocin的化学合成，以及与它的另一种天然单糖基化形式的drosocin的结构和功能特性的比较，即α-GalNAc-drosocin以及非糖基化的drosocin。相对于所有测试的革兰氏阴性细菌，与单糖基化drosocin相比，含drosocin的二糖显示出较低的效力，表明远端糖的作用或糖链长度增加对活性的影响。圆二色性研究未能证明糖对整体肽构象的差异作用。由于糖链长度的增加，drosocin的溶血和细胞毒性特性没有改变。此外，我们还评估了差异糖基化drosocins对鼠巨噬细
• Revealing Functional Significance of Interleukin‐2 Glycoproteoforms Enabled by Expressed Serine Ligation
  作者：Jie Zhao、Jiazhi Liu、Xinnan Liu、Qi Cao、Hongbo Zhao、Lizhen Liu、Farong Ye、Can Wang、Hong Shao、Dongxiang Xue、Houchao Tao、Bin Li、Biao Yu、Ping Wang

  DOI：10.1002/cjoc.202100914

  日期：2022.4

  Herein, to stress this issue, we report a highly efficient semi-synthesis of homogeneous glycosylated IL-2 with various glycoproteoforms on a multi-milligram scale. The glycopeptide fragment was prepared by chemical synthesis and then merged with recombinant fragment via a serine ligation to generate the desired glycoprotein in a single operation. Biological evaluation of the homogenous glycoprotein library

  天然存在的白细胞介素 2 (IL-2) 是一种多效性糖蛋白，通过控制 T 细胞的分化和稳态来调节免疫反应。非糖基化 IL-2 已在临床环境中使用了 30 年。然而，天然 IL-2 的O-聚糖的功能仍然难以捉摸。在此，为了强调这个问题，我们报告了一种高效的半合成同质糖基化 IL-2 与多种糖蛋白形式的数毫克规模。糖肽片段通过化学合成制备，然后通过重组片段与重组片段融合丝氨酸连接，在一次操作中生成所需的糖蛋白。同源糖蛋白库的生物学评价表明，IL-2在激活个体T细胞亚群中的活性是聚糖依赖性的，从而突出了进一步改进当前临床医学的可能性。
• Synthesis and characterization of natural and modified antifreeze glycopeptides: glycosylated foldamers
  作者：Lilly Nagel、Carolin Plattner、Carsten Budke、Zsuzsanna Majer、Arthur L. DeVries、Thomas Berkemeier、Thomas Koop、Norbert Sewald

  DOI：10.1007/s00726-011-0937-8

  日期：2011.8

  biological antifreeze agents are crucial for the survival of polar fish. One group of such agents is classified as antifreeze glycoproteins (AFGP) that usually consist of a varying number (n = 4–55) of [AAT] n -repeating units. The threonine side chain of each unit is glycosidically linked to β-d-galactosyl-(1 → 3)-α-N-acetyl-d-galactosamine. These biopolymers can be considered as biological antifreeze foldamers

  在北极和南极海洋地区，温度下降到生理液的依数凝固点以下，有效的生物防冻剂对于极地鱼类的生存至关重要。这类试剂中的一组被归类为抗冻糖蛋白（AFGP），通常由不同数量（n  = 4–55）的[AAT] n重复单元组成。每个单元的苏氨酸侧链与β- d-半乳糖基-（1→3）-α - N-乙酰基-d糖基连接 -半乳糖胺。这些生物聚合物可以被认为是生物防冻折叠剂。AFGP逐步合成的制备途径可实现高效合成。使用微波增强的固相合成将二糖基化的苏氨酸结构单元引入肽中。通过这种通用的固相方法，可以获得不同序列和长度的糖基化肽。合成的AFGP类似物的构象研究是通过圆二色性实验（CD）进行的。此外，根据折叠剂对冰的再结晶的抑制作用和对晶体习性的影响，对折叠剂进行了微观分析。