ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Development of transition state analogue inhibitors for N-acetylglycosyltransferases bearing D-psicoor D-tagatofuranose scaffolds

Marek Baráth, Chun-Hung Lin, Igor Tvaroška, and Ján Hirsch

Institute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, 845 38 Bratislava, Slovakia

E-mail: marek.barath@savba.sk

Abstract: New potential transition state analogue inhibitors for N-acetylglucosyltransferases (GnTs) were synthesised. These compounds based on psico- and tagatofuranose (structure) scaffold contained a 2-thiophenyl-1-O-diethylphosphate moiety mimicking the proposed model of the transition state of the enzymatic reaction catalysed by N-acetylglucosyltransferases. The synthesised compounds as well as their precursors were fully characterised by NMR, optical rotation and mass techniques. Anomeric configuration of tagatofuranose derivatives was confirmed by X-ray crystallography. Two types of potential human glycosyltransferase (GnTs) inhibitors representing donor UDP-GlcNAc, assigned for biological assays on human GnTs, were prepared.

Keywords: glycosyltransferases – inhibitors – tagatofuranoside – psicofuranoside – transition state mimetic – X-ray crystalography

Full paper is available at www.springerlink.com.

DOI: 10.1515/chempap-2015-0063

Chemical Papers 69 (2) 348–357 (2015)