benzyl O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-galactopyranosyl)-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-serinate | 100929-03-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzyl O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-galactopyranosyl)-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-serinate
• 英文别名: N-(fluoren-9-ylmethoxycarbonyl)-(2-acetamido-deoxy-3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-L-serine benzyl ester；N-(fluoren-9-ylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-serine benzyl ester；N-(9-fluorenylmethyloxycarbonyl)-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-galactopyranosyl)-L-serine benzyl ester；benzyl (2S)-3-[(2S,3R,4R,5R,6R)-3-acetamido-4,5-diacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoate
• CAS: 100929-03-1
• 化学式: C₃₉H₄₂N₂O₁₃
• 分子量: 746.768
• InChiKey: YFHLTVVKNQMZBT-OWRFXFELSA-N

物化性质

• 沸点：
  899.9±65.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.31
• 重原子数：
  54.0
• 可旋转键数：
  14.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  191.09
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  benzyl O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-galactopyranosyl)-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-serinate 在 palladium on activated charcoal 吗啉 、 2-isobutoxy-1-isobutoxycarbonyl-1,2-dihydroquinoline 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 114.0h， 生成
  参考文献：
  名称：

  Synthetic and Immunological Studies on Clustered Modes of Mucin-Related Tn and TF O-Linked Antigens:  The Preparation of a Glycopeptide-Based Vaccine for Clinical Trials against Prostate Cancer

  摘要：

  The syntheses of two tumor-associated carbohydrate antigens, Tn and TF, have been achieved using glycal assembly and cassette methodologies. These synthetic antigens were subsequently clustered (c) and immunoconjugated to a carrier protein (KLH or BSA) or a synthetic lipopeptide (pam) for immunological study. Three Tn conjugates were used to vaccinate groups of mice, and all preparations proved to be immunogenic. The Tn(c) covalently linked to KLH (27-KLH) plus the adjuvant QS-21 was the optimal vaccine, inducing high median IgM and IgG titers against Tn(c) by ELISA. These antibodies were strongly reactive with the Tn(c) positive human colon cancer cell line LS-C but not the Tn(c) negative colon cancer cell Line LS-B by FAGS. The antibodies' reactivities with natural antigens were inhibited with synthetic Tn(c) but not with structurally unrelated compounds. On the basis of these results, vaccines containing 27-KLH and 30-pam plus QS-21 are being tested in patients with prostate cancer.

  DOI：

  10.1021/ja9825128
• 作为产物：
  描述：

  3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-galactopyranosyl chloride 在 硼酸 、 nickel dichloride 吡啶 、 calcium sulfate 、 sodium tetrahydroborate 、 3 A molecular sieve 、 silver carbonate 作用下， 反应 8.5h， 生成 benzyl O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-galactopyranosyl)-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-serinate
  参考文献：
  名称：

  具有TN和T抗原结构的糖肽的合成及其与牛血清白蛋白的偶联。

  摘要：

  合成了具有TN和T抗原结构的糖肽，这些肽代表具有血型M特异性的去唾液酸糖蛋白的N端三肽，已使用芴基甲氧基羰基（Fmoc）和2-吡啶基乙氧基羰基（Pyoc）基团进行氨基保护，并使用苄基酯作为羧基封闭基团来合成糖肽功能。Fmoc和Pyoc基团可以通过在碱敏感的O-糖基丝氨酸和-苏氨酸键稳定的条件下用弱碱吗啉处理而除去。用甲醇肼从碳水化合物部分除去酯基，得到TN和T抗原糖肽，其通过碳二亚胺方法与牛血清白蛋白（BSA）偶联，并且没有任何间隔基。所得的缀合物每个蛋白质分子平均包含大于20个糖肽。

  DOI：

  10.1016/0008-6215(90)84081-5

文献信息

• Cowpea Mosaic Virus Capsid: A Promising Carrier for the Development of Carbohydrate Based Antitumor Vaccines
  作者：Adeline Miermont、Hannah Barnhill、Erica Strable、Xiaowei Lu、Katherine A. Wall、Qian Wang、M. G. Finn、Xuefei Huang

  DOI：10.1002/chem.200800203

  日期：2008.5.29

  Immunotherapy targeting tumor cell surface carbohydrates is a promising approach for cancer treatment. However, the low immunogenecity of carbohydrates presents a formidable challenge. We describe here the enhancement of carbohydrate immunogenicity by an ordered display on the surface of the cowpea mosaic virus (CPMV) capsid. The Tn glycan, which is overexpressed on numerous cancer cell surfaces, was

  针对肿瘤细胞表面碳水化合物的免疫疗法是一种有前途的癌症治疗方法。然而，碳水化合物的低免疫原性提出了巨大的挑战。我们在这里描述了通过豇豆花叶病毒（CPMV）衣壳表面的有序展示来增强碳水化合物的免疫原性。 Tn 聚糖在许多癌细胞表面过度表达，被选为我们研究的模型抗原。此前已有研究表明，针对不同载体上以多种方式呈现的单体形式的 Tn，很难诱导出强烈的 T 细胞依赖性免疫反应。在这项研究中，我们首先合成了由马来酰亚胺或溴乙酰胺部分衍生的 Tn 抗原，该部分选择性地与 CPMV 的半胱氨酸突变体缀合。然后将糖缀合物注射到小鼠体内，并通过酶联免疫吸附测定法测量免疫前和免疫后小鼠血清中的抗体水平。在免疫后第 35 天的血清中获得了高总抗体滴度，更重要的是，高 Tn 特异性 IgG 滴度，表明糖缀合物诱导了 T 细胞依赖性抗体同种型转换。生成的抗体能够识别 MCF-7 乳腺癌细胞和多药耐药乳腺癌细胞系 NCI-ADR
• In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues
  作者：Ryuma Sakura、Kaori Nagai、Yuka Yagi、Yoshihisa Takahashi、Yoshimi Ide、Yuki Yagi、Daiki Yamamoto、Mamoru Mizuno、Toshinori Sato

  DOI：10.1016/j.carres.2021.108495

  日期：2022.1

  synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells. Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion. The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers

  已知蛋白质中丝氨酸或苏氨酸残基的粘蛋白型O-糖基化是主要的翻译后修饰之一。在这项研究中，两种新型烷基糖苷，N α -lauryl - O -(2-acetamido-2-deoxy-α- d -galactopyranosyl ) -l -serineamide (GalNAc-Ser-C12) 和N α -lauryl - O- (2-acetamido-2-deoxy-α- d -galactopyranosyl ) -l -threonineamide (GalNAc-Thr-C12) 作为糖类引物合成O型粘蛋白-细胞中的聚糖生物合成。用糖类引物孵育人胃癌 MKN45 细胞后，获得了 22 种糖基化产物，并使用液相色谱-质谱法和酶消化法分析了它们的结构。糖基化产物的量取决于糖类引物中的氨基酸残基。例如，体外T 抗原 (Galβ1-3GalNAc)、岩藻糖基-T (Fucα1-2Galβ1-3GalNAc)
• [EN] COMPOSITIONS AND METHODS OF TREATING CANCER AND INFECTIONS USING BACTERIOPHAGE AND ITS MUTANTS<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DU CANCER ET DES INFECTIONS À L'AIDE D'UN BACTÉRIOPHAGE ET DE SES MUTANTS
  申请人：UNIV MICHIGAN STATE

  公开号：WO2019045791A1

  公开（公告）日：2019-03-07

  Provided herein are vaccine composition comprising an antigen conjugated to a capsid, wherein the capsid comprises wild type or native sequence. Provided herein are also vaccine composition comprising an antigen conjugated to a capsid, wherein said capsid comprises at least one mutation, such as a non-natural mutation. Such compositions are useful in the treatment and prevention of pathogenic infections, inflammatory diseases, and neurodegenerative disease, and cancer, among others.

  本文提供了一种疫苗组合物，包括与壳蛋白共轭的抗原，其中壳蛋白包括野生型或天然序列。本文还提供了一种疫苗组合物，包括与壳蛋白共轭的抗原，其中所述壳蛋白包括至少一种突变，如非自然突变。这些组合物在治疗和预防病原体感染、炎症性疾病、神经退行性疾病和癌症等方面非常有用。
• Syntheses of α-d-galactosamine neoglycolipids
  作者：Nicolas Laurent、Dominique Lafont、Paul Boullanger

  DOI：10.1016/j.carres.2006.02.013

  日期：2006.5

  Several N-acetyl-alpha-D-galactosamine neoglycolipids, as well as hydrophobized T and T-N antigen analogues, were prepared for embedment onto liposomes. Three different lipidic structures were used for the anchoring, that is cholesterol, 1,3-bis(undecyloxy)propan-2-ol and 1, 3-bis(3,7,11,15-tetramethyl hexadecyloxy) propan-2-ol. Oligoethyleneglycol spacers were used to link the carbohydrate and the hydrophobic moieties; their lengths were varied in order to obtain model compounds for the selective recognition by sialyl transferases involved in cancer processes. Glycosylation reactions were optimized to sluggish amphiphilic acceptor alcohols, in order to reach good 1,2-cis-stereoselectivities and acceptable yields. This aim was achieved by using 3,4,6-tri-O-acetyl-2-azido-2deoxy-D-galactopyranosyl trichloroacetimidate as the donor, trimethylsilyl trifluoromethanesulfonate as the promoter and diethyl ether or mixtures of diethyl ether and dichloromethane as solvents. (c) 2006 Elsevier Ltd. All rights reserved.
• α-Selective glycosylation affords mucin-related GalNAc amino acids and diketopiperazines active on Trypanosoma cruzi
  作者：Maristela B. Martins-Teixeira、Vanessa L. Campo、Monica Biondo、Renata Sesti-Costa、Zumira A. Carneiro、João S. Silva、Ivone Carvalho

  DOI：10.1016/j.bmc.2013.01.027

  日期：2013.4

  This work addresses the synthesis and biological evaluation of glycosyl diketopiperazines (DKPs) cyclo[Asp-(alpha GalNAc)Ser] 3 and cyclo[Asp-(alpha GalNAc)Thr] 4 for the development of novel anti-trypanosomal agents and Trypanosoma cruzi trans-sialidase (TcTS) inhibitors. The target compounds were synthetized by coupling reactions between glycosyl amino acids alpha GalNAc-Ser 7 or alpha GalNAc-Thr 8 and the amino acid (O-tBu)-Asp 17, followed by one-pot deprotection-cyclisation reaction in the presence of 20% piperidine in DMF. The protected glycosyl amino acid intermediates 7 and 8 were, in turn, obtained by a-selective, HgBr2-catalysed glycosylation reactions of Fmoc-Ser/Thr benzyl esters 12/14 with alpha GalN(3)Cl 11, being, subsequently, fully deprotected for comparative biological assays. The DKPs 3 and 4 showed relevant anti-trypanosomal effects (IC50 282-124 mu M), whereas glycosyl amino acids 1 and 2 showed better TcTS inhibition (57-79%) than the corresponding DKPs (13-25%). (C) 2013 Elsevier Ltd. All rights reserved.