Glycoconjugates play a key role in cell-cell recognition and interaction process. They are also responsible for such events as inflammation, tumor metastasis, bacterial or viral infection or immune system activation. In synthesis of glycoconjugates in biological system enzymes such as glycosidases and glycosyltransfrases are involved. Glycosyltransferases of the Leloir pathway are key enzymes responsible for synthesis of most cell-surface glcoconjugates in mammalian systems. They catalyze the transfer of a sugar moiety from an activated nucleotide sugar to the hydroxyl group of an acceptor which may be a growing oligosaccharide, a lipid or a protein [1]. Inhibition of these enzyme leads to the modulation of oligosaccharide biosynthesis and enables us to study their biological functions. Therefore some of such inhibitors might be of therapeutic interest.

Recently we presented synthesis of some kind of analogues of sugar nucleotides, which were designed to act as glycosyltransferases inhibitors particularly donor substrate analogues [2]. In these glycoconjugates aryl- or heteroaryl 1-thioglycosides derivatives of D-glucose or D-galactose were connected to selectively protected uridine by amide bond with or without a spacer. Some of them exhibited antiviral activity against classical swine fever virus (CSFV) [3]. Now we present next part of our research on changes in structure of already synthesized glycoconjugates and their influence on biological activity of obtained compounds. We add one more sugar unit (derivative of glucose or 2-iodo-2-deoxy mannose) to earlier synthesized glycoconjugates. We also try to construct analogues of glycosyltransferases natural substrates by changing configuration at the anomeric centre of (5-nitro-2-pyridyl) 1-thioglycosides used to connection to uridine derivatives.

Acknowledgement

Research studies part-financed by European Union Structural Funds in Poland (UDA-POKL.04.01.01-00-114/09-00).

[1] Jung, K. H.; Schmidt, R. R. Glycosyltransferase Inhibitors in: „Carbohydrate-Based Drug Discovery”, C.-H. Wong (Ed.), Wiley-VCH, 2003, 23, 609-659   

[2] Pastuch-Gawołek G.; Bieg T.; Szeja W.; Flasz J.; Bioorg. Chem. 2009, 37, 77-83

[3] Szewczyk, B.; Tyborowska, J.; Krol, E.; Szeja, W.; J. Biotechnol., 2005, 118S1, S84-S85

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