Glycosidases in Carbohydrate Synthesis: When Organic Chemistry Falls Short

Bojarová, Pavla; Křen, Vladimı́r

doi:10.2533/chimia.2011.65

Cited by 29 publications

(16 citation statements)

References 70 publications

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“…Furthermore, synthetic method of glycoproteins containing N-linked sugar chains by using the reversed reaction of Endo M by Yamamoto et al 104) has tremendously been developed in recent years, 105,106) and it is now possible to obtain even a glycoprotein, which has no micro-heterogeneity in its sugar moieties, and opening a gate for the comparative study of a glycoprotein with different N-linked sugar chains. I would like to present two representative reviews 107,108) for the readers who are interested in this newly developing field.…”

Section: Discussionmentioning

confidence: 99%

Exo- and endoglycosidases revisited

Kobata

2013

Proc. Jpn. Acad., Ser. B

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Many glycosidases, which work as useful reagents for the studies of structures and functions of free and conjugated oligosaccharides, have been found and thoroughly purified. These enzymes are classified into exo- and endoglycosidases by their glycon specificities. Their usefulness and limits as reagents are explained in detail in this review.Endoglycosidases, which were originally found in the culture fluid of bacteria and in the extracts of plants, are now widely found in the mammals including humans. The physiological roles of these enzymes are discussed in relation to the oligosaccharides accumulated in the urine of patients with exoglycosidase deficiencies. Furthermore, PNGase is found to play important roles in the ER-associated degradation pathway of glycoproteins.Recent studies of the glycosidases in Bifidobacteria have revealed that GNB/LNB pathway, which uniquely exist in this bacteria, works for the expression of Bifidus factor activity of human milk oligosaccharides, an important topic in the baby nutrition. This interesting field will be introduced in detail in one section of this article.

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Section: Discussionmentioning

confidence: 99%

Exo- and endoglycosidases revisited

Kobata

2013

Proc. Jpn. Acad., Ser. B

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“…In the last 100 years, glycosidase-catalyzed synthesis has developed from simple glycosylations of alcohols to one-pot multienzyme processes, [48] tailored enzyme mutants, [49] and boldly derivatized substrates as building blocks of saccharides with direct medicinal or biotechnological applications. [50] Glycosidase-assisted synthesis and mechanisms have recently been examined in several reviews. [51][52][53][54] It is to be emphasized that an important aspect of the industrial application of glycosidases consists in targeted trimming of long, natural polysaccharide chains, thus producing either the desired small active compound directly or embodied in a set of defined derivatives of increasing molecular weight (e.g., di-, tri-, tetrasaccharides, etc.).…”

Section: Glycoside Hydrolasesmentioning

confidence: 99%

Enzymatic Glycosylation of Small Molecules: Challenging Substrates Require Tailored Catalysts

Desmet

Soetaert

Bojarová

et al. 2012

Chemistry A European J

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193

194

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Glycosylation can significantly improve the physicochemical and biological properties of small molecules like vitamins, antibiotics, flavors, and fragrances. The chemical synthesis of glycosides is, however, far from trivial and involves multistep routes that generate lots of waste. In this review, biocatalytic alternatives are presented that offer both stricter specificities and higher yields. The advantages and disadvantages of different enzyme classes are discussed and illustrated with a number of recent examples. Progress in the field of enzyme engineering and screening are expected to result in new applications of biocatalytic glycosylation reactions in various industrial sectors.

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“…The highly biocompatible glycan-decorated HPMA copolymers described in this work are predestined for in vivo application. In this work we present an efficient chemoenzymatic synthesis [ 33 ] of the selective LacdiNAc disaccharide epitope bearing various functionalities using the Tyr470His mutant of the β- N -acetylhexosaminidase from Talaromyces flavus developed in our laboratory [ 34 ]. We have thoroughly analyzed the impact of structural organization and the type of conjugation of LacdiNAc disaccharide on the binding of the HPMA glycopolymers to Gal-3.…”

Section: Introductionmentioning

confidence: 99%

Biocompatible glyconanomaterials based on HPMA-copolymer for specific targeting of galectin-3

et al. 2018

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BackgroundGalectin-3 (Gal-3) is a promising target in cancer therapy with a high therapeutic potential due to its abundant localization within the tumor tissue and its involvement in tumor development and proliferation. Potential clinical application of Gal-3-targeted inhibitors is often complicated by their insufficient selectivity or low biocompatibility. Nanomaterials based on N-(2-hydroxypropyl)methacrylamide (HPMA) nanocarrier are attractive for in vivo application due to their good water solubility and lack of toxicity and immunogenicity. Their conjugation with tailored carbohydrate ligands can yield specific glyconanomaterials applicable for targeting biomedicinally relevant lectins like Gal-3.ResultsIn the present study we describe the synthesis and the structure-affinity relationship study of novel Gal-3-targeted glyconanomaterials, based on hydrophilic HPMA nanocarriers. HPMA nanocarriers decorated with varying amounts of Gal-3 specific epitope GalNAcβ1,4GlcNAc (LacdiNAc) were analyzed in a competitive ELISA-type assay and their binding kinetics was described by surface plasmon resonance. We showed the impact of various linker types and epitope distribution on the binding affinity to Gal-3. The synthesis of specific functionalized LacdiNAc epitopes was accomplished under the catalysis by mutant β-N-acetylhexosaminidases. The glycans were conjugated to statistic HPMA copolymer precursors through diverse linkers in a defined pattern and density using Cu(I)-catalyzed azide–alkyne cycloaddition. The resulting water-soluble and structurally flexible synthetic glyconanomaterials exhibited affinity to Gal-3 in low μM range.ConclusionsThe results of this study reveal the relation between the linker structure, glycan distribution and the affinity of the glycopolymer nanomaterial to Gal-3. They pave the way to specific biomedicinal glyconanomaterials that target Gal-3 as a therapeutic goal in cancerogenesis and other disorders.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0399-1) contains supplementary material, which is available to authorized users.

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Glycosidases in Carbohydrate Synthesis: When Organic Chemistry Falls Short

Cited by 29 publications

References 70 publications

Exo- and endoglycosidases revisited

Exo- and endoglycosidases revisited

Enzymatic Glycosylation of Small Molecules: Challenging Substrates Require Tailored Catalysts

Biocompatible glyconanomaterials based on HPMA-copolymer for specific targeting of galectin-3

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