Glycosyl azide—a novel substrate for enzymatic transglycosylations

Fialová, Pavla; Carmona, Ana T.; Robina, Inmaculada; Ettrich, Rüdiger; Sedmera, Petr; Přikrylová, Věra; Petrásková, Lucie; Křen, Vladimı́r

doi:10.1016/j.tetlet.2005.10.040

Cited by 44 publications

(47 citation statements)

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“…This can be explained by a huge molar excess of acceptor (5-6:1) as well as by a too low concentration of donor in reaction mixture ( 100 mM) for autocondensation reactions. [7] Conclusions This work clearly demonstrates the potential of glycosyl azides as donors in transglycosylation reactions with various glycosidases. The screening for hydrolytic cleavage revealed that the respective glycosyl azides are fairly well cleaved by b-galactosidases, b-glucosidases and a-mannosidases, contrary to the tested agalactosidases, which were substantially inhibited by the azide 1.…”

Section: Introductionmentioning

confidence: 60%

“…Despite the close chemical resemblance to glycosyl fluorides, no "wrong anomer hydrolysis" [6] was observed during the cleavage of glycosyl azides. Azides are cleaved more slowly than the corresponding p-nitrophenyl glycosides [7] and glycosyl fluorides [8] (considering k cat , K M ), however, they do not inhibit the enzyme at higher concentrations and afford good transglycosylation yields, probably due to the reduction of water activity by the high donor concentration. Their chemical behaviour was thoroughly described by Gyçrgy-deàk and Thiem.…”

Section: Introductionmentioning

confidence: 99%

“…[12] We have used 2-acetamido-2-deoxy-b-d-glucopyranosyl and -galactopyranosyl azide in transglycosylation reactions with b-N-acetylhexosaminidases. [7] In this paper we exploit the versatility of glycosyl azides as donors in transglycosylation reactions with a representative sample of various glycosidases: a-and b-galactosidases, b-glucosidases, and a-mannosidases. Three enzyme classes, b-galactosidases, b-glucosidases, and a-mannosidases, proved to be good catalysts for synthesis with glycosyl azides.…”

Section: Introductionmentioning

confidence: 99%

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Glycosyl Azides – An Alternative Way to Disaccharides

et al. 2007

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This paper is dedicated to the memory of Prof. Zoltµn Gyçrgydeàk, who greatly contributed to the chemistry of glycosyl azides.Abstract: Glycosyl azides are shown to be efficient donors for b-galactosidases, b-glucosidases and amannosidases. Only a-galactosidases do not cleave the respective glycosyl azide 1 and, moreover, they exhibit competitive inhibition (especially a-galactosidase from Talaromyces flavus). High water solubility and ready synthesis of glycosyl azides enable transglycosylation reactions even with difficult acceptors like N-acetyl-d-mannosamine in good yields. The versatility of glycosyl azides was demonstrated in the synthesis of five disaccharides -two of them are described for the first time. All the reactions were highly regioselective, yielding bA C H T U N G T R E N N U N G (1!6) isomers. bGalactosidase from E. coli proved to have the best synthetic capabilities. The present study shows that glycosyl azides are a valuable alternative to common p-nitrophenyl glycoside donors and in many synthetic reactions.

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Section: Introductionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glycosyl Azides – An Alternative Way to Disaccharides

et al. 2007

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“…[3] Previously, we have demonstrated that fungal b-N-acetylhexosaminidases possess a wide tolerance to substrates bearing various modifications, including N-acyls, [4] sulfates, [5] and an absent C-4 hy-droxy. [6] Moreover, GlcNAc substrates with two unusual C À N linked aglycones, namely the azido group [7] and the aromatic triazole moiety, [8] were cleaved by some fungal b-N-acetylhexosaminidases; the azide even worked as an efficient glycosyl donor in transglycosylation reactions. [7] As for the biological and especially the immunomodulatory activity of glycosides and glycoconjugates, our previous studies described the ability of N-acetyld-hexosamine structures to stimulate the immune response: they can activate natural killer (NK) cells by binding to their activation receptors, such as NKR-P1 and CD69 proteins.…”

Section: Introductionmentioning

confidence: 99%

“…[6] Moreover, GlcNAc substrates with two unusual C À N linked aglycones, namely the azido group [7] and the aromatic triazole moiety, [8] were cleaved by some fungal b-N-acetylhexosaminidases; the azide even worked as an efficient glycosyl donor in transglycosylation reactions. [7] As for the biological and especially the immunomodulatory activity of glycosides and glycoconjugates, our previous studies described the ability of N-acetyld-hexosamine structures to stimulate the immune response: they can activate natural killer (NK) cells by binding to their activation receptors, such as NKR-P1 and CD69 proteins. [9] A significantly enhanced binding affinity was observed in structures bearing negatively charged functional groups such as carboxyl or sulfate, [9a,10] but no systematic study on this phenomenon has been presented until now.…”

Section: Introductionmentioning

confidence: 99%

Charged Hexosaminides as New Substrates for β‐N‐Acetylhexosaminidase‐Catalyzed Synthesis of Immunomodulatory Disaccharides

et al. 2011

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This work is a structure-activity relationship study that investigates the influence of the nature and amount of negative charge in carbohydrate substrates on the affinity of b-N-acetylhexos-A C H T U N G T R E N N U N G aminidases, and on the stimulation of natural killer cells. It describes synthetic procedures yielding novel glycosides that are useful in immunoactivation. Specifically, we present a thorough study on the ability of six C-6 modified b-N-acetylhexosaminides (aldehyde, uronate, 6-O-sulfate, 6-O-phosphate) to serve as substrates for cleavage and glycosylation by a library of b-N-acetylhexosaminidases from various sources. Four novel disaccharides with one or two (negatively) charged groups were prepared in synthetic reactions in good yields. Surprisingly, the 6-Ophosphorylated substrate, although cleaved by a number of enzymes from the series, worked neither as a donor nor as an acceptor in transglycosylation reactions. The results of wet experiments were supported by molecular modeling of substrates in the active site of two representative enzymes from the screening. All ten prepared compounds were examined in terms of their immunoactivity, namely as ligands of two activation receptors of natural killer (NK) cells, NKR-P1 and CD69, both with isolated proteins and whole cells. Sulfated disaccharides in particular acted as very efficient protectants of NK cells against activation-induced apoptosis, and as stimulants of the natural killing of resistant tumor cells, which makes them good candidates for potential clinical use in cancer treatment.

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Enzymatic Synthesis of Glycosides and Glucuronides

Scaffidi

Křen²,

Bojarová

et al. 2009

Practical Methods for Biocatalysis and Biotransformations

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Glycosidases are enzymes that effectively catalyse the cleavage of the glycosidic linkage of some of the most structurally diverse substrates in nature. Removal of the catalytic nucleophile of retaining glycosidases, through site-directed mutagenesis, results in an enzyme unable to cleave glycosidic linkages but with the ability to form them. 1 There have been numerous glycosynthases produced over the years and they have become versatile tools in preparing complex oligosaccharides that could otherwise not be easily achieved using traditional methods. 2 Recently, preparation of the biologically active glycosylated derivatives of 2-deoxy-2-fluoro--laminaribiosyl fluoride, along with the use of inositols as substrates, has been reported. 3,4 1. A small piece of Na was added to MeOH (5 mL) and the resulting solution was added to tetra-O-acetyl--D-glucopyranosyl fluoride (130 mg, 0.37 mmol) and 4,6-di-Oacetyl-2-deoxy-2-fluoro-3-O-(tetra-O-acetyl--D-glucopyranosyl)--D-glucosyl fluoride (44 mg, 0.07 mmol) in MeOH (5 mL) and the solution stirred (1 h) before being neutralized with Amberlite resin IR-120 (H þ ), filtered and concentrated to afford a colourless residue. 2. This residue was then dissolved in NH 4 HCO 3 solution (150 mM, 25 mL), followed by the addition of Abg E358G (0.2 mg), and the solution kept at 25°C for 2 days. The solvent was removed under reduced pressure and the residue treated with Ac 2 O (2 mL, 21 mmol) and pyridine (5 mL) containing DMAP (5 mg) and stirred at 50°C for 3 h. The reaction was quenched with MeOH (10 mL) and concentrated. The residue was dissolved in saturated NaHCO 3 solution (25 mL) and dichloromethane (25 mL). The dichloromethane layer was separated, dried over anhydrous MgSO 4 , filtered and concentrated using a rotary evaporator. 3. Purification by flash chromatography (EtOAc/petrol, 2:3-3:2) furnished the trisaccharide as a powder (35 mg, 54 %), m.p. 93-95°C, [] D ¼ À4.5°. 1 H NMR (500 MHz) 1.99-2.14 (27H, 8s, CH 3 ), 3.62 (ddd, J 4 0 , 5 0 9.9, J 5 0 , 6 0 4.7, 1.9, H5 0 ), 3.65 (dd, J 4 00 , 5 00 9.9, (9C, C¼O). m/z (high resolution mass spectrometry fast atom bombardment (HR-MS FAB)) 887.2632; [M þ H] þ requires 887.2633. 4. Next to elute was the tetrasaccharide as a powder (25 mg, 29 %), m.p. 108-110°C, [] D ¼ À6.8°. Partial 1 H NMR (500 MHz) [a] 1.97-2.15 (36H, 11s, CH 3 ), 3.57 (ddd,

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Glycosyl azide—a novel substrate for enzymatic transglycosylations

Cited by 44 publications

References 19 publications

Glycosyl Azides – An Alternative Way to Disaccharides

Glycosyl Azides – An Alternative Way to Disaccharides

Charged Hexosaminides as New Substrates for β‐N‐Acetylhexosaminidase‐Catalyzed Synthesis of Immunomodulatory Disaccharides

Enzymatic Synthesis of Glycosides and Glucuronides

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