Rational Design of Inhibitors Targeting Human Sialyltransferases

Sialic acids are negatively charged sugars that are often located at the terminal end of glycan chains on cell surface and secreted molecules, allowing them to play crucial roles in cellular biology. Sialyltransferases are enzymes of the glycosyltransferase family that play an integral role in the biosynthesis of sialic acid containing oligosaccharides and glycoconjugates. Abnormal sialylation is strongly associated with cancer, with hypersialylation of up to 30–40% observed, along with significant upregulation of sialyltransferase activity. This has been directly correlated with an increased metastatic potential of tumours, avoidance of apoptotic pathways and resistance to therapy..