Glycosylation is one of the most important post-translational modification of gene products and is often critical to specific cellular biological functions. It is well proven that sugars binding to lipids and proteins on the cell surface participate in various intercellular and intracellular events such as cell-cell interactions, cell adhesion, inflammation, immune system response, they take part in tumor metastasis and both viral and parasitic infections [1]. Because of the importance of glycosylation in biological systems glycosyltransferases are interesting targets for the development of their specific inhibitors which might have the potential to precisely modify the structures of any class of cell-surface glycoconjugate. For this reason, considerable effort has been directed toward the design of glycosyltransferase inhibitors [2, 3]. The development of inhibitors of glycosyltranferase may lead to discovery of novel therapeutics for the treatment of certain diseases in which carbohydrates-protein interactions are involved [4].

Synthesis of GTs donor type natural substrate analogues, in which carbohydrate moiety is connected to aromatic aglycon (nitropyridine derivative) via 1-α-thioglycosidic bond is very challenging and purification of final products can cause many difficulties. Our recent research led us to utilize 1,6-anhydrosugars in the synthesis of optically pure 1-α-thioglycosides and their use as glycoconjugates building blocks. The anomeric centre configuration of the synthesized compounds is identical to the anomeric centre of the natural substrate of β-1,4-galactosyltransferase [5]. Final glycoconjugates are expected to control and modulate activity of investigated enzymes.

Acknowledgement :

Research studies part-financed by the European Union within the Structural Funds in Poland (POIG.01.01.02-14-102/09). Roman Komor received a scholarship under the project DoktoRIS - Scholarship Program for Innovative Silesia.

References:

[1] Weijers, C.; Franssen, M.; Visser, G. Biotechnol. Adv. 2008, 26, 436.

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

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

[4] Roseman, S., J. Biol. Chem., 2001, 276, 41527–41542.

[5] Komor, R.; Pastuch-Gawołek, G.; Sobania, A.; Jadwiński, M., Acta Poloniae Pharmaceutica - Drug Research, 2012, 69, 1259-1269.

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