Glycosyltransferases as targets for therapeutic intervention in cancer and inflammation: molecular modeling insights

Glycans are fundamental constituents of all cells. Glycans biosynthesis, glycosylation, is a key post-translational modification that affects most proteins. Glycosylation engages a class of glycosyltransferases that transfer glycosyl residue from a donor containing a nucleoside phosphate to an acceptor molecule. Enormous heterogeneity of glycans carries biological information decoded by a family of adhesion glycoproteins called lectins, including selectins, galectins, and Siglecs. There is a growing body of evidence that aberrant glycosylation modulates functions in physiological and pathological states of inflammatory diseases and the development and progression of cancer. Therefore, glycans have obvious potential as therapeutic targets for anti-inflammatory and anti-cancer drugs. This review focuses on glycosyltransferases involved in N -, and O -glycosylation, their structure, catalytic mechanism, and strategies toward developing glycosyltransferase inhibitors that have potential as therapeutics in inflammation and cancer. Graphical abstract