Targeting Glycosylation with Chemical Tools Seminar

Glycosyltransferases (GTs) are Nature’s glycosylation reagents: enzymes that catalyse the transfer of a mono- or oligosaccharide from a glycosyl donor to a suitable acceptor, e.g. a glycan, peptide or lipid. GTs play a key role in many fundamental biological processes underpinning human health and disease, including cell wall biosynthesis in pathogenic bacteria and cellular adhesion in mammals. Individual GTs have been identified as promising therapeutic targets in infection, inflammation and cancer [1], and inhibitors and chemical probes for GTs are therefore of considerable scientific interest for chemical biology and drug discovery.

The Wagner group has a long-­‐standing interest in the development of chemical tool compounds for GT research. Recent examples include the discovery of a novel type of allosteric GT inhibitor [2], the development of fluorescent probes for mammalian and bacterial galactosyltransferases [3], and the identification of drug-­‐ like inhibitors for mannosyltransferases from the human parasite T. brucei [4]. In this presentation, a brief introduction to the biological and therapeutic relevance of GTs will be followed by selected examples from ongoing research in the Wagner group in this area, with a particular focus on recent work on bacterial GTs.

[1] (a) ChemBioChem 2010, 11, 1939-1949; (b) MedChemComm 2014, 5, 1106‐1125 (special issue on “Carbohydrates in Medicinal Chemistry”);

[2] (a) Nature Chem. Biol. 2010, 6, 321‐323; (b) J. Med. Chem. 2012, 55, 2015‐2024; (c) J. Biol. Chem. 2013, 288, 26201‐26208;

[3] (a) ChemBioChem 2010, 11, 1392‐1398; (b) Org. Biomol. Chem. 2011, 9, 1855‐1863;

[4] (a) Bioorg. Med. Chem. Lett. 2009, 19, 1749‐1752; (b) Org. Biomol. Chem. 2010, 8, 3488‐3499

All welcome to attend