102039-79-2Relevant academic research and scientific papers
Novel sequential solid-phase synthesis of N-linked glycopeptides from natural sources
Meinjohanns, Ernst,Meldal, Morten,Paulsen, Hans,Dwek, Raymond A.,Bock, Klaus
, p. 549 - 560 (1998)
In the present report a practical and versatile procedure for the solid-phase synthesis of N-linked glycopeptides from natural sources has been demonstrated. The approach is based on the mild hydrazinolysis procedure to release N-linked oligosaccharides in their intact unreduced form from the natural glycoproteins, e.g. fetuin and ribonuclease B and subsequent formation of the corresponding glycosylamines. Treatment of the reducing sugars 1-7 with a saturated solution of ammonium hydrogen carbonate in either water or dimethyl sulfoxide (DMSO) gives in almost quantitative yields the glycosylamines 8-14. Coupling of the unprotected glycosylamines 8-14 to the side-chain-activated aspartic acid derivative Fmoc-Asp(ODhbt)-OBut 16 affords the N-glycosylated asparagine derivatives 17-23. Subsequent acetylation of the carbohydrate hydroxy groups and cleavage of the tert-Bu ester by trifluoroacetic acid (TFA) treatment yields the glycosylated N-linked building blocks 31-37. The building blocks 31-37 are then incorporated into the multiple-column peptide-synthesis protocol of the glycopeptide T-cell epitope analogues 40-46 of the mouse haemoglobin-derived decapeptide Hb (67-76), VITAFNEGLK. The decapeptide sequence VITAFNEGLK binds well to the MHC Class II Ek molecule and is non-immunogenic in CBA/J mice. Syntheses of several natural and unnatural glycosylations, e.g. N-acetylglucosamine, N,N′-diacetylchitobiose, glucose, maltotriose, maltoheptose and di- and triantennary complex oligosaccharides on the decapeptide Hb (67-76) affording the N-linked glycopeptides 40-46 are described. The N-linked glycopeptides 40-46 have been fully characterised by 1D- and 2D-1H and 13C NMR spectroscopy and by ES-MS.
A fluorometric assay for glycosyltransferase activities using sugars aminated and tagged with 7-hydroxycoumarin-3-carboxylic acid as substrates and high performance liquid chromatography
Higai, Koji,Masuda, Daisuke,Matsuzawa, Yukinari,Satoh, Tamae,Matsumoto, Kojiro
, p. 333 - 338 (1999)
We developed a novel fluorometric assay method for the measurement of glycosyltransferase activities using mono- and di-saccharides aminated and tagged with 7-hydroxycoumarin-3-carboxylic acid (coumarin) as substrates, N- acetylglucosamine (GlcNAc)-coumarin for β1,4-galactosyltransferase from bovine milk and Galβ1-4GlcNAc-coumarin for α2,3- and α2,6- sialyltransferases from rat liver. Using Galβ1-3GlcNAc and Galβ1-4GlcNAc- coumarin, α1, 3/4 /4- and 1/4 ,3-fucosyltransferase activities were also determined, respectively. These enzymatic products liberated by the reactions of glycosyltransferases in the presence of sugar nucleotides, were separated by a normal phase or an ion-pair reversed phase HPLC with an isocratic elution and fluorescence detection. We applied this assay method to determine the glycosyltransferase activities in 8 kinds of human tumor cell lines, including the cell lines derived from hepatocytes (HuH-7, HepG2), colonic cells (Colo205, HT-29), myelocytes (HL-60, U-937), B-lymphocytes (Daudi) and T-lymphocytes (Jurkat). This assay method is accurate and easy compared with other isotopic and non-isotopic assay methods, and is sensitive enough to measure glycosyltransferase activities in cell homogenates.
α-Glucopyranoimidazolines as intermediate analogue inhibitors of family 20 β-N-acetylglucosaminidases
Kato, Masahiro,Uno, Tetsuya,Hiratake, Jun,Sakata, Kanzo
, p. 1563 - 1571 (2005)
The α-glucopyranoimidazolines, 2-methyl-(1,2-dideoxy-α-D- glucopyrano)[2,1-d]-1-imidazolines 1 and 2, have been synthesized and evaluated as inhibitors of β-N-acetylglucosaminidases (NAGs). Compounds 1 and 2, mimicking the oxazolinium ion intermediate in
Synthesis of Artificial N-Glycopolypeptides Carrying N-Acetyllactosamine and Related Compounds and Their Specific Interactions with Lectins
Zeng, Xiaoxiong,Murata, Takeomi,Kawagishi, Hirokazu,Usui, Taichi,Kobayashi, Kazukiyo
, p. 1171 - 1178 (1998)
Artificial N-glycopolypeptides carrying N-acetyllactosamine (LacNAc) or related compounds were synthesized. First, sugars were converted into their corresponding β-glycosylamines with ammonium hydrogen carbonate. Then, the β-glycosylamines were condensated with the carboxyl groups of poly(L-glutamic acid). N-Glycopolypeptides with different degrees of substitution of sugars were isolated by passage through a column of Sephadex G-25. These synthetic polymers were used as model compounds in the analysis of oligosaccharide-lectin interactions. Interactions with some lectins were investigated by agar-gel double-diffusion tests and in terms of inhibition of hemagglutination. A glycopolypeptide substituted with LacNAc reacted with Erythrina cristagalli agglutinin (ECA), peanut (Arachis hypogaea) agglutinin (PNA), Ricinus communis agglutinin-120 (RCA120), wheat germ (Triticum vulgaris) agglutinin (WGA) lectins, which recognize either galactosyl or N-acetylglucosamine (GlcNAc) residues. Other synthetic glycopolymers carrying N-acetylisolactosamine, GlcNAc, N,N′-diacetylchitobiose, or N,N′,N″-triacetylchitotriose also reacted with WGA, and these last two polymers inhibited hemagglutination most. Of these five glycopolypeptides, only the one substituted with LacNAc reacted with ECA. These sugar-substituted glycopolypeptides interacted specifically with the corresponding lectins, no matter how much shorter the sugar side chains of the glycopolymers were than those of natural glycoproteins.
Total Synthesis of Glycosylated Human Interferon-γ
Ashhurst, Anneliese S.,Dowman, Luke J.,Fairbanks, Antony J.,Kwan, Ann,Larance, Mark,Li, Henry Y.,Payne, Richard J.,Wang, Xiaoyi,Watson, Emma E.
, p. 6863 - 6867 (2020)
Interferon-γ(IFN-γ) is a glycoprotein that is responsible for orchestrating numerous critical immune induction and modulation processes and is used clinically for the treatment of a number of diseases. Herein, we describe the total chemical synthesis of homogeneously glycosylated variants of human IFN-γusing a tandem diselenide-selenoester ligation-deselenization strategy in the C- to N-terminal direction. The synthetic glycoproteins were successfully folded, and the structures and antiviral functions were assessed.
N-Linked Glycosyl Auxiliary-Mediated Native Chemical Ligation on Aspartic Acid: Application towards N-Glycopeptide Synthesis
Chai, Hua,Le Mai Hoang, Kim,Vu, Minh Duy,Pasunooti, Kalyan,Liu, Chuan-Fa,Liu, Xue-Wei
, p. 10363 - 10367 (2016)
A practical approach towards N-glycopeptide synthesis using an auxiliary-mediated dual native chemical ligation (NCL) has been developed. The first NCL connects an N-linked glycosyl auxiliary to the thioester side chain of an N-terminal aspartate oligopeptide. This intermediate undergoes a second NCL with a C-terminal thioester oligopeptide. Mild cleavage provides the desired N-glycopeptide.
Convergent Synthesis of N-Linked Glycopeptides via Aminolysis of ω-Asp p-Nitrophenyl Thioesters in Solution
Du, Jing-Jing,Gao, Xiao-Fei,Xin, Ling-Ming,Lei, Ze,Liu, Zheng,Guo, Jun
, p. 4828 - 4831 (2016)
An efficient N-linked glycosylation reaction between glycosylamines and p-nitrophenyl thioester peptides has been developed. The reaction conditions are mild and compatible with the C-terminal free carboxylic acid group and the unprotected N-linked sialyl
Mixed SAMs and MALDI-ToF MS: Preparation of N-glycosylamine derivative and thioctic acid methyl ester bearing 1,2-dithiolane groups and detection of enzymatic reaction on Au
Hassan, Hani Mutlak A.,Maltman, Beatrice A.
, p. 6 - 9 (2012)
Herein, we report an enzymatic galactosylation reaction of β-glucopyranosylamide 4 and thioctic acid methyl ester 5 bearing 1,2-dithiolane groups to form a new system of mixed self-assembled monolayers (SAMs) on gold. Characterization of the enzymatic activity was conveniently achieved by mass spectrometry.
Chemoenzymatic synthesis and lectin array characterization of a class of N-glycan clusters
Huang, Wei,Wang, Denong,Yamada, Masao,Wang, Lai-Xi
, p. 17963 - 17971 (2009)
N-Glycans are major components of many glycoproteins. These sugar moieties are frequently involved in important physiological and disease processes via their interactions with a variety of glycanbinding proteins (GBP). Clustering effect is an important feature in many glycan-lectin interactions. We describe in this paper a chemoenzymatic synthesis of novel N-glycan clusters using a tandem endoglycosidase-catalyzed transglycosylation. It was found that the internal β-1,2-linked GlcNAc moieties in the N-glycan core, once exposed in the nonreducing terminus, was able to serve as acceptors for transglycosylation catalyzed by Endo-A and EndoM-N175A. This efficient chemoenzymatic method allows a quick extension of the sugar chains to form a class of glycan clusters in which sugar residues are all connected by native glycosidic linkages found in natural N-glycans. In addition, a discriminative enzymatic reaction at the two GlcNAc residues could be fulfilled to afford novel hybrid clusters. Lectin microarray studies revealed unusual properties in glyco-epitope expression by this panel of structurally well-defined synthetic N-glycans. These new compounds are likely valuable for functional glycomics studies to unveil new functions of both glycans and carbohydrate-binding proteins.
A Tripeptide Approach to the Solid-Phase Synthesis of Peptide Thioacids and N-Glycopeptides
Sch?we, Markus Julian,Keiper, Odin,Unverzagt, Carlo,Wittmann, Valentin
, p. 15759 - 15764 (2019)
A general and robust method for the incorporation of aspartates with a thioacid side chain into peptides has been developed. Pseudoproline tripeptides served as building blocks for the efficient fluorenylmethyloxycarbonyl (Fmoc) solid-phase synthesis of t
