68733-26-6Relevant articles and documents
Synthesis aided structural determination of amyloid-β(1-15) glycopeptides, new biomarkers for Alzheimer's disease
Wang, Peng,Nilsson, Jonas,Brinkmalm, Gunnar,Larson, G?ran,Huang, Xuefei
, p. 15067 - 15070 (2014)
Unique tyrosine glycosylated amyloid-β(1-15) glycopeptides were synthesized with well-defined stereochemistry at the glycosidic linkages. Aided by these glycopeptides and tandem mass spectrometry analysis, the naturally existing amyloid-β glycopeptides, isolated from Alzheimer's disease patients, were determined to contain an α-linked N-acetyl galactosamine at the modified tyrosine 10 residue. Glycosylation can significantly impact the properties of amyloid-β as the glycopeptide has much lower affinity for Cu+ ions.
In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues
Sakura, Ryuma,Nagai, Kaori,Yagi, Yuka,Takahashi, Yoshihisa,Ide, Yoshimi,Yagi, Yuki,Yamamoto, Daiki,Mizuno, Mamoru,Sato, Toshinori
, (2022/01/14)
Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications. In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-threonineamide (GalNAc-Thr-C12) were 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. For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue. Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments. These results indicate that glycosyltransferases involved in the biosynthesis of mucin-type O-glycans distinguish amino acid residues conjugated to GalNAc. The saccharide primers developed in this study might be useful for comparing mucin-type oligosaccharides in cells and constructing oligosaccharide libraries to study cell function.
Enhanced Binding and Reduced Immunogenicity of Glycoconjugates Prepared via Solid-State Photoactivation of Aliphatic Diazirine Carbohydrates
Congdon, Molly D.,Gildersleeve, Jeffrey C.
, p. 133 - 142 (2021/01/09)
Biological conjugation is an important tool employed for many basic research and clinical applications. While useful, common methods of biological conjugation suffer from a variety of limitations, such as (a) requiring the presence of specific surface-exposed residues, such as lysines or cysteines, (b) reducing protein activity, and/or (c) reducing protein stability and solubility. Use of photoreactive moieties including diazirines, azides, and benzophenones provide an alternative, mild approach to conjugation. Upon irradiation with UV and visible light, these functionalities generate highly reactive carbenes, nitrenes, and radical intermediates. Many of these will couple to proteins in a non-amino-acid-specific manner. The main hurdle for photoactivated biological conjugation is very low yield. In this study, we developed a solid-state method to increase conjugation efficiency of diazirine-containing carbohydrates to proteins. Using this methodology, we produced multivalent carbohydrate-protein conjugates with unaltered protein charge and secondary structure. Compared to carbohydrate conjugates prepared with amide linkages to lysine residues using standard NHS conjugation, the photoreactive prepared conjugates displayed up to 100-fold improved binding to lectins and diminished immunogenicity in mice. These results indicate that photoreactive bioconjugation could be especially useful for in vivo applications, such as lectin targeting, where high binding affinity and low immunogenicity are desired.
Stereoselective Synthesis of 1,1′-Disaccharides by Organoboron Catalysis
Izumi, Sanae,Kobayashi, Yusuke,Takemoto, Yoshiji
, p. 14054 - 14059 (2020/06/10)
The highly stereoselective synthesis of 1,1′-disaccharides was achieved by using 1,2-dihydroxyglycosyl acceptors and glycosyl donors in the presence of a tricyclic borinic acid catalyst. In this reaction, the complexation of the diols and the catalyst is
Synthesis of trisaccharide repeating unit of fucosylated chondroitin sulfate
He, Haiqing,Chen, Dong,Li, Xiaomei,Li, Chengji,Zhao, Jin-Hua,Qin, Hong-Bo
supporting information, p. 2877 - 2882 (2019/03/21)
We described the chemical synthesis of a sulfated trisaccharide repeating unit of fucosylated chondroitin sulfate (FCS), which has significant anticoagulant activity. Well-functionalized monosaccharides were readily prepared, and highly efficient glycosyl
A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine
Riedl, Bettina,Schmid, Walther
supporting information, p. 856 - 860 (2018/04/30)
Synthetic approaches towards N-acetylgalactosamine (GalNAc) have been attracting considerable interest since this compound is known for its pivotal role in cell-cell interaction and receptor induced cell signaling. Herein, we present a synthetic route in which two of the four stereogenic centers present in the target compound are derived from enantiopure tartaric acid being selectively converted to epoxy alcohols. The key step is the Pd-catalyzed, stereo- and regioselective epoxide opening and subsequent nucleophilic substitution of an azide functionality. This approach enables the synthesis of the naturally D- and unnaturally L-configured GalNAc, as well as both enantiomers of the largely unknown N-acetylidosamine (IdoNAc).
Synthesis method and application of sialylated TF antigen and its fluorination derivatives
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Paragraph 0054; 0069; 0071-0073, (2018/07/07)
The invention discloses a synthesis method and an application of a sialylated TF antigen and its fluorination derivatives. The method includes the following steps: (1) chemically synthesizing fluorogalactose and fluorogalactosamine analogues; (2) chemically synthesizing a fluorinated TF antigen; and (3) synthesizing the sialylated TF antigen and its fluorination derivatives through an enzyme technology. The flexibility of a chemical synthesis technology is combined with the high regioselectivity and the high efficiency of the enzyme synthesis technology, so the enzymatic synthesis of the fluorosialylated TF antigen is achieved for the first time, and the disadvantages of many synthesis steps, poor stereoselectivity, low yield and use of a heavy metal salt in existing chemical synthesis ofthe fluorosialylated TF antigen are overcome. A fluorotumor-associated carbohydrate antigen has a higher stability than natural carbohydrate antigen, so the sialylated TF antigen and its fluorinationderivatives have a broad application prospect in the development of novel antitumor vaccines.
Tn antigen and synthesis process thereof
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Paragraph 0078; 0080; 0096; 0098; 0109; 0111, (2017/05/25)
The invention provides a synthesis process of a Tn antigen and relates to the field of biological medicine. The synthesis process includes the steps that firstly, a donor and a receptor are subjected to a glycosylation reaction under the catalytic action of trimethylsilyl trifluoromethanesulfonate to generate glucoside, the first location of the donor is replaced and protected by phenyl trifluoroacetyl imidogen, the second location is replaced and protected by an azide group, the sixth location is replaced and protected by p-nitrobenzoyl, and the receptor is 1-benzyl-2-fluorene acyl-serine/threonine; then, all groups of the glucoside are converted, and the Tn antigen is generated. The synthesis process is simple in process, complete alpha selection can be achieved, and the yield of the Tn antigen is raised. The invention further provides the Tn antigen, and the Tn antigen is high in purity and can be used for preparing a cancer vaccine.
Synthesis of di- and tri-saccharide fragments of Salmonella typhi Vi capsular polysaccharide and their zwitterionic analogues
Fusari, Matteo,Fallarini, Silvia,Lombardi, Grazia,Lay, Luigi
supporting information, p. 7439 - 7447 (2015/11/27)
Zwitterionic polysaccharides (ZPS) behave like traditional T cell-dependent antigens, suggesting the design of new classes of vaccines alternative to currently used glycoconjugates and based on the artificial introduction of a zwitterionic charge motif onto the carbohydrate structure of pathogen antigens. Here we report the new synthesis and antigenic evaluation of di-/tri-saccharide fragments of Salmonella typhi Vi polysaccharide, as well as of their corresponding zwitterionic analogues. Our strategy is based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approach using disaccharide donors. The effect of structural modifications of the synthetic compounds on antigenic properties was evaluated by competitive ELISA. All the oligosaccharides were recognized by specific anti-Vi polyclonal antibodies in a concentration-dependent manner, and the introduction of a zwitterionic motif into the synthetic molecules did not prevent the binding.
Synthesis of the tumor associative α-aminooxy disaccharide of the TF antigen and its conjugation to a polysaccharide immune stimulant
Bourgault, Jean Paul,Trabbic, Kevin R.,Shi, Mengchao,Andreana, Peter R.
, p. 1699 - 1702 (2014/03/21)
The α-aminooxy derivative of the Thomsen-Friedenriech tumor associated carbohydrate antigen has been synthesized in 11 steps utilizing a d-GalN3 acceptor carrying a pre-installed α-N- hydroxysuccinimidyl moiety. The natural α linkage was prepar
