Glycosyltransferases (GTs) are enzymes involved in the synthesis and modification of the multitude of glycoconjugates that exist in the biosphere. They typically act by adding monosaccharides one at a time to specific positions on specific precursors. The biosynthesis of glycans is primarily determined by these sequentially acting enzymes, which assemble monosaccharides into linear and branched sugar chains [1]. In general GTs catalyze transglycosylation reactions where the monosaccharide component of a high-energy nucleotide sugar donor (e.g., GDP-Fuc or CMP-Sia) is transferred to a precursor – acceptor, forming glycosidic bonds. The result of glycosyl transfer can be a glycoside, oligo- or polysaccharide. Glycosyl transfer can also occur to protein residues, may also use lipids as an acceptor, forming glycolipids, or even lipid-linked sugar phosphate donors [2,3]. GTs donor type natural substrates generally consist of three different moieties that can be distinguished: carbohydrate part, diphosphate linkage and nucleoside moiety (mostly uridine).

Inhibition of glycosyltransferases have an enormous significance in controlling of synthesis of cell-surface glycoconjugates. It leads to the modulation of oligosaccharides biosynthesis and enables recognition of their biological functions. Therefore some inhibitors of GTs may be interesting from therapeutic point of view.

Our previous research on glycosyltransferases inhibitors revealed biological activity of these connections against classical swine fever virus (CSFV) [4,5]. Our recent research led us to obtain glycoconjugates derivatives of D-glucose, D-galactose, 2-deoxy-D-glucose and 2-deoxy-D-galactose including α-1-thioglycosidic part connected to selectively protected uridine through the amide bond. Improvement of the synthesis and investigation of the biological activity are in progress.

Research studies part-financed by the European Union within the Structural Funds in Poland  (POIG.01.01.02-14-102/09). Roman Komor was supported by European Funds (POKL.04.01.01-00-114/09-01).

1. Weijers C., Franssen M., Visser G.: Biotechnol. Adv. 26, 436 (2008).

2. Jung K.H., Schmidt R.R. Glycosyltransferase Inhibitors in: Carbohydrate-Based Drug Discovery, C.-H. Wong Eds, p. 609, Wiley-VCH, 2003.

3. Varki A, Cummings R, Esko J Glycosyltransferases in: Essentials of Glycobiology, Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press, 1999.

4. G. Pastuch-Gawołek; T. Bieg; W. Szeja; J. Flasz, Bioorganic Chemistry 2009, 37, 77-83.

5. G. Pastuch; R. Komor; M. Grec; W. Szeja, Acta Poloniae Pharmaceutica - Drug Research  2010, 67, 642-651.

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