XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Lectures
SYNTHESIS OF GLCNaC-TS MIMETICS AS a POTENT INHIBITORS OF
GLYCOSYLTraNSFEraSES
Marek Baráth, Igor Tvaroška and Ján Hirsch
Institute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, 845 38
Bratislava, Slovakia
Glysosyltransferases are enzymes that catalyst transfer of monosacharidic unit from an
activated sugar phosphate to an acceptor molecule, usually an alcohol. The result of
glycosyl transfer can be a monosaccharide glycoside, an oligosaccharide or polysaccharide.
Many functions have been implicated for protein glycosylation, including promoting
protein folding or stabilizing cell-surface glycoproteins.
Different strategies have been used in order to identify potent inhibitors of glycosyltransferases.
The main goal of this contribution is to synthesized of the transition state
(TS) analogs starting from the donor UDP-GlcNAc. A leading idea of all these TS analogs
is a „ 1-thio“ linker between a mimetic of GlcNAc in TS geometry and a mimetic of the
acceptor bearing the β-D-psicofuranose, β-D-tagatofuranose and backbones with the
key substitution on position C-1 by the phosphate group and on position C-2 by the
thiophenyl group, which has been designed.
Couple of potential inhibitors have been synthesized bearing β-D-psico and β-D-tagato
configuration using a multi step synthesis. The β-D-psico analogs were as well as utilized
for the synthesis of N-acetylated β-D-fructo analogs as their epimers in three more steps
using a Walden inversion at C-3 position.
Acknowledgement: This work was partially supported by the grants: VEGA 2/6129/27,
2/0128/08 and Centre of Excelence- GLYCOMED.
44 XXII. Biochemistry Congress, Martin