- Applications of Shoda's reagent (DMC) and analogues for activation of the anomeric centre of unprotected carbohydrates
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2-Chloro-1,3-dimethylimidazolinium chloride (DMC, herein also referred to as Shoda's reagent) and its derivatives are useful for numerous synthetic transformations in which the anomeric centre of unprotected reducing sugars is selectively activated in aqueous solution. As such unprotected sugars can undergo anomeric substitution with a range of added nucleophiles, providing highly efficient routes to a range of glycosides and glycoconjugates without the need for traditional protecting group manipulations. This mini-review summarizes the development of DMC and some of its derivatives/analogues, and highlights recent applications for protecting group-free synthesis.
- Fairbanks, Antony J.
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- NOVEL IMMUNODULATING SMALL MOLECULES
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The present invention includes novel compositions and methods for treating comprising a compound with the Formula I: where n = 0-5; X = NH, O, S, CH2; Y = Phenyl, a phenyl group substituted with at least one methyl, a phenyl group substituted with at least one nitro, a phenyl group substituted with at least one nitrogen, a phenyl group substituted with at least one boron, aryl, substituted aryl, heteroaryl, four to six membered cycloalkyl, four to six membered heterocycloalkyl; R = H, C(O)R2, SO2R2; R1 = H, C(O)R2, SO2R2; R2 = Ethyl, methyl, isopropyl, n-propyl, t-butyl, n- butyl, NH2, NR3R4; R3, R4 = Ethyl, methyl, isopropyl, n-propyl, t-butyl, n-butyl, three to six membered cycloalkyl and Z = NH, O, S, CH2 or none, wherein the amount of the compound is selected to either inhibit or activate the immune response.
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Paragraph 0188; 0193
(2020/01/31)
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- Scope of the DMC mediated glycosylation of unprotected sugars with phenols in aqueous solution
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Activation of reducing sugars in aqueous solution using 2-chloro-1,3-dimethylimidazolinium chloride (DMC) and triethylamine in the presence of para-nitrophenol allows direct stereoselective conversion to the corresponding 1,2-Trans para-nitrophenyl glycosides without the need for any protecting groups. The reaction is applicable to sulfated and phosphorylated sugars, but not to ketoses or uronic acids or their derivatives. When applied to other phenols the product yield was found to depend on the pKa of the added phenol, and the process was less widely applicable to 2-Acetamido sugars. For 2-Acetamido substrates an alternative procedure in which the glycosyl oxazoline was pre-formed, the reaction mixture freeze-dried, and the crude product then reacted with an added phenol in a polar aprotic solvent system with microwave irradiation proved to be a useful simplification.
- Fairbanks, Antony J.,Qiu, Xin
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p. 7355 - 7365
(2020/10/13)
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- Direct Synthesis of para-Nitrophenyl Glycosides from Reducing Sugars in Water
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Reducing sugars may be directly converted into the corresponding para-nitrophenyl (pNP) glycosides using 2-chloro-1,3-dimethylimidazolinium chloride (DMC), para-nitrophenol, and a suitable base in aqueous solution. The reaction is stereoselective for sugars with either a hydroxyl or an acetamido group at position 2, yielding the 1,2-trans pNP glycosides. A judicious choice of base allows extension to di-and oligosaccharide substrates, including a complex N-glycan oligosaccharide isolated from natural sources, without the requirement of any protecting group manipulations
- Fairbanks, Antony J.,Qiu, Xin
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supporting information
(2020/03/24)
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- Facile Formation of β-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase
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Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes. The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A). This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors. Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields. The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
- Tegl, Gregor,Hanson, John,Chen, Hong-Ming,Kwan, David H,Santana, Andrés G.,Withers, Stephen G.
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supporting information
p. 1632 - 1637
(2019/01/14)
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- ABIOTIC ANTI-VEGF NANOPARTICLE
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The present invention relates generally to compositions and methods comprising abiotic, synthetic polymers with affinity and specificity to proteins. The synthetic polymers are an improvement over biological agents by providing a simpler, less expensive, and customizable platform for binding to proteins. In one embodiment, the compositions and methods relate to synthetic polymers with affinity and specificity to vascular endothelial growth factor (VEGF). In one embodiment, the compositions are useful for treating diseases and disorders related to the overexpression of VEGF. In one embodiment, the compositions are useful for treating cancer. In one embodiment, the compositions are useful for detecting VEGF levels from biological samples. In one embodiment, the compositions are useful for detecting overexpression of VEGF from biological samples. In one embodiment, the compositions are used to diagnose cancer.
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Page/Page column 30
(2018/09/25)
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- Glycosynthase with broad substrate specificity-an efficient biocatalyst for the construction of oligosaccharide library
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A versatile glycosynthase (TnG-E338A) with strikingly broad substrate scope has been developed from Thermus nonproteolyticus β-glycosidase (TnG) by using site-directed mutagenesis. The practical utility of this biocatalyst has been demonstrated by the facile generation of a small library containing various oligosaccharides and a steroidal glycoside (total 25 compounds) in up to 100 % isolated yield. Moreover, an array of eight gluco-oligosaccharides has been readily synthesized by the enzyme in a one-pot, parallel reaction, which highlights its potential in the combinatorial construction of a carbohydrate library that will assist glycomic and glycotherapeutic research. Significantly, the enzyme provides a means by which glycosynthase technology may be extended to combinatorial chemistry.
- Wei, Jinhua,Lv, Xun,Lue, Yang,Yang, Gangzhu,Fu, Lifeng,Yang, Liu,Wang, Jianjun,Gao, Jianhui,Cheng, Shuihong,Duan, Qian,Jin, Cheng,Li, Xuebing
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p. 2414 - 2419
(2013/05/23)
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- Facile synthesis of nitrophenyl 2-acetamido-2-deoxy-α-D- mannopyranosides from ManNAc-oxazoline
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The synthetic procedures for a large-scale preparation of o- and p-nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranoside are described. The synthetic pathway employs the glycosylation of phenol with ManNAc oxazoline, followed by nitration of the aromatic moiety yielding a separable mixture of the o- and p-nitrophenyl derivative in a 2:3 ratio.
- Krenek, Karel,Simon, Petr,Weignerova, Lenka,Fliedrova, Barbora,Kuzma, Marek,Kren, Vladimir
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experimental part
p. 428 - 432
(2012/05/05)
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- Characterization of a novel Salmonella Typhimurium chitinase which hydrolyzes chitin, chitooligosaccharides and an N-acetyllactosamine conjugate
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Salmonella contain genes annotated as chitinases; however, their chitinolytic activities have never been verified. We now demonstrate such an activity for a chitinase assigned to glycoside hydrolase family 18 encoded by the SL0018 (chiA) gene in Salmonella enterica Typhimurium SL1344. A C-terminal truncated form of chiA lacking a putative chitin-binding domain was amplified by PCR, cloned and expressed in Escherichia coli BL21 (DE3) with an N-terminal (His)6 tag. The purified enzyme hydrolyzes 4-nitrophenyl N,N′-diacetyl - d-chitobioside, 4-nitrophenyl -d-N,N′,N″-triacetylchitotriose and carboxymethyl chitin Remazol Brilliant Violet but does not act on 4-nitrophenyl N-acetyl - d-glucosaminide, peptidoglycan or 4-nitrophenyl -d-cellobioside. Enzyme activity was also characterized by directly monitoring product formation using 1H-nuclear magnetic resonance which showed that chitin is a substrate with the release of N,N′-diacetylchitobiose. Hydrolysis occurs with the retention of configuration and the enzyme acts on only the -anomers of chitooligosaccharide substrates. The enzyme also released N-acetyllactosamine disaccharide from Gal1 → 4GlcNAc-O-(CH2)8CONH(CH 2)2NHCO-tetramethylrhodamine, a model substrate for LacNAc terminating glycoproteins and glycolipids.
- Larsen, Tanja,Petersen, Bent O.,Storgaard, Birgit G.,Duus, Jens,Palcic, Monica M.,Leisner, Jorgen J.
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scheme or table
p. 426 - 436
(2012/01/13)
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- Syntheses of p-nitrophenyl 3- and 4-thio-β-d-glycopyranosides
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Thioglycosides have proved to be useful, enzymatically stable analogs of glycosides for structural and mechanistic studies and their synthesis is considerably simplified through the use of thioglycoligases. As part of an investigation into the use of thio
- Chen, Hong-Ming,Withers, Stephen G.
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experimental part
p. 2596 - 2604
(2011/01/12)
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- Syntheses of the 3- and 4-thio analogues of 4-nitrophenyl 2-acetamido-2-deoxy-β-d-gluco- and galactopyranoside
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The syntheses of 4-nitrophenyl β-glycosides of the 3-thio and 4-thio analogues of the two principal 2-acetamido-2-deoxy-hexoses found in living systems, GlcNAc and GalNAc, are described. While synthesis of the 4-thio analogues could be achieved via nucleophilic displacements of sulfonate derivatives with thioacetate, problems with neighbouring group acetamido participation necessitated the use of sulfamidate intermediates for the 3-thio analogues. These 3- and 4-thio analogues are employed in the chemo-enzymatic synthesis of thio-oligosaccharide analogues of structures present in glycosaminoglycans, glycoproteins and glycolipids.
- Chen, Hong-Ming,Withers, Stephen G.
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p. 2212 - 2222
(2008/02/12)
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- Cyanodeoxy-glycosyl derivatives as substrates for enzymatic reactions
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Synthetic routes for the preparation of new sugar nitriles 8-10 derived from 2-acetamido-2-deoxy-β-D-glucopyranosides bearing a cyano group at the C-5 or C-6 position are presented. In an attempt to prepare the glycosyl azide 10 by treatment of tosylate 23 with KCN/DMF at 60°C, an intramolecular 1,3-dipolar cycloaddition reaction occurred to give the highly constrained nonisolable tetrazole 24, which was readily converted into the imino-azido compound 25 through an azido-tetrazole tautomerism. Compounds 8 and 10 were found to be poorer substrates of fungal β-N-acetylhexosaminidases than compound 9 and none of these compounds was accepted as substrates of the nitrilase or nitrile hydratase. Docking of the nitriles 8-10 in the active site of the β-N-acetylhexosaminidase from Aspergillus oryzae gave interaction energies comparable with the natural substrate. Based on these data, which indicate strong binding of these compounds (8 > 9 > 10) to the active site, it has been proposed that some cyano derivatives may act as competitive inhibitors of β-N-acetylhexosaminidases. This hypothesis is consistent with enzyme inhibition experiments which showed strong inhibitory properties of compound 9 (KI = 0.37 mM) and in particular of compound 8 (KI = 7.6 μM). Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Carmona, Ana T.,Fialova, Pavla,Kren, Vladimir,Ettrich, Rudiger,Martinkova, Ludmila,Moreno-Vargas, Antonio J.,Gonzalez, Cristina,Robina, Inmaculada
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p. 1876 - 1885
(2007/10/03)
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- A concise synthesis of 4-nitrophenyl 2-azido-2-deoxy- and 2-acetamido-2-deoxy-d-mannopyranosides
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4-Nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α- and β-d-mannopyranosides were prepared from methyl 4,6-O-benzylidene-α-d- glucopyranoside and 1,3,4,6-tetra-O-acetyl-α-d-glucopyranose, respectively. Chemoselective reduction of both azides with hydrogen sulfide readily afforded 4-nitrophenyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-α-d- and -β-d-mannopyranosides in higher yields than reduction with triphenylphosphine or a polymer-supported triarylphosphine. Subsequent de-O-acetylation yielded 4-nitrophenyl 2-acetamido-2-deoxy-α-d- mannopyranoside and 4-nitrophenyl 2-acetamido-2-deoxy-β-d-mannopyranoside in 20% and 44% overall yields, respectively.
- Popelová, Alena,Kefurt, Karel,Hlavá?ková, Martina,Moravcová, Jitka
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p. 161 - 166
(2007/10/03)
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- Synthesis of 4-nitrophenyl 2-acetamido-2-deoxy-β-D-mannopyranoside and 4-nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranoside
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The title compounds were synthesized by the selective reduction of the azido group in 4-nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-mannopyranoside (8) and 4-nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-mannopyranoside (11), and by subsequent acetylation. Compound 8 was prepared by opening of the epoxide ring in methyl 2,3-anhydro-4,6-O-benzylidene-α-D-glucopyranoside (1) with sodium azide, followed by inversion of the configuration at C-3 in the resulting altropyranoside and glycosidation with 4-nitrophenol.
- Krist, Pavel,Kuzma, Marek,Pelyvas, Istvan F.,Simerska, Pavla,Kren, Vladimir
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p. 801 - 811
(2007/10/03)
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- Glycosidase-catalysed oligosaccharide synthesis: preparation of N-acetylchitooligosaccharides using the β-N-acetylhexosaminidase of Aspergillus oryzae
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The β-N-acetylhexosaminidase of Aspergillus oryzae catalyses the formation of 2-acetamido-4-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-2-deoxy-D-glucopyranose (di-N-acetylchitobiose) and 2-acetamido-6-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-2-deoxy-D-glucopyranose from p-nitrophenyl 2-acetamido-2-deoxy-β-D-glucopyranoside and 2-acetamido-2-deoxy-D-glucopyranose.The ratio of the two disaccharides is time-dependent.The ratio of (14)- to (16)-isomers is a maximum (ca. 9:1) at the point of disappearance of the glycosyl donor.If left to evolve, the ratio changes to 92:8 in favour of the (16)-isomer.Either the (14)- or the (16)-isomer can be isolated by treating the appropriately enriched disaccharide mixture with the β-N-acetylhexosaminidase of Jack bean (Canavalia ensiformis) or the β-N-acetylhexosaminidase of A. oryzae, respectively.Di-N-acetylchitobiose is an efficient donor of 2-acetamido-2-deoxy-D-glucopyranosyl units in reactions catalysed by the N-acetylhexosaminidase of A. oryzae.Di-N-acetylchitobiose itself acts as acceptor to give tri-N-acetylchitotriose .As the trisaccharide accumulates it, in turn, acts as acceptor giving tetra-N-acetylchitotetraose .The product mixture consisting of mono-, di-, tri-, and tetra-saccharides is conveniently separated by charcoal-Celite chromatography. Keywords: Glycosidase; N-acetylhexosaminidase; Chitooligosaccharides; Enzymatic synthesis.
- Singh, Suddham,Packwood, John,Samuel, Christopher J.,Critchley, P.,Crout, David H. G.
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p. 293 - 306
(2007/10/03)
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- Carbohydrate protein interactions. Syntheses of agglutination inhibitors of wheat germ agglutinin by phase transfer catalysis
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Starting from chloride 1, a series of para-substituted aryl 2-acetamido-2-deoxy-β-D-glucopyranosides were prepared using phase transfer catalysis conditions with tetrabutylammonium hydrogen sulfate in 1 M sodium hydroxide and methylene chloride at room temperature.Zemplen de-O-acetylation afforded the unprotected glycosides.Optimization of reaction conditions was evaluated.Several functional group manipulations were effected to widen the number and nature of the para-substituents. Key words: phase transfer catalysis, aryl 2-acetamido-2-deoxy-β-D-glucopyranosides.
- Roy, Rene,Tropper, Francois D.
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p. 817 - 821
(2007/10/02)
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- Syntheses and Transformations of Glycohydrolase Substrates into Protein Conjugates Based on Michael Additions
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The glycosyl chloride 1 and bromides 2 and 3 were stereospecifically transformed into p-nitrophenyl glycosides by phase transfer catalysis; these glycohydrolase substrates were reduced and N-acryloylated to afford Michael acceptors which reacted with amine functions of proteins.
- Roy, Rene,Tropper, Francois D.,Morrison, Tara,Boratynski, Janusz
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p. 536 - 538
(2007/10/02)
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- Properties and Transglycosylation Reaction of a Chitinase from Nocardia orientalis
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The hydrolytic products of a chitinase purified from Nocardia orientalis were examined on reduced (GlcNAc)n (n=2-6).The rate of hydrolysis on reduced (GlcNAc)4-6 increased with increasing chain-length of N-acetylglucosamine residues,
- Nanjo, Fumio,Sakai, Kazuo,Ishikawa, Masato,Isobe, Kiyoshi,Usui, Taichi
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p. 2189 - 2195
(2007/10/02)
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