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Chemical Biology

A supplement providing a snapshot of the latest developments in chemical biology

Sialyl transferase inhibition could help treat cancer

09 February 2006

A new type of cell-permeable sialyltransferase inhibitor that could lead to the development of new approaches in cancer treatment has been discovered by chemists in Taiwan.

"This approach provides a simple way to the design of new and optimal sialyltransferase inhibitors (or prodrugs) for clinical investigation"
- Wen-Shan Li

Wen-Shan Li and colleagues from the Academia Sinica and National Taiwan Normal University have developed new lithocholic acid analogue inhibitors whose structures are based on an authentic sialyltransferase inhibitor obtained from random screening of several thousand compounds. Until now few sialyltransferase inhibitors with cell-permeable properties have been found.

Sialyltransferases are involved in the biosynthesis of biologically important molecules known as sialylated glycoconjugates. This process involves catalysing the transfer of sialic acids to terminal positions of oligosaccharide chains of glycoconjugates. Increased sialyltransferase activity results in hypersialylation of these glycoconjugates. This is significant in certain biological processes including the spread of tumour cells, cell adhesion and inflammation. Inhibiting the activity of sialyltransferases modifies these processes and could open up new therapeutic possibilities such as the development of new approaches to cancer treatment.

Synthesis of an alpha-2,3-sialyltransferase inhibitor

There are about twenty different sialyltransferases that catalyse sialic acids to glycans. The challenge faced in the future will be to develop selective and cell-permeable inhibitors of these different sialyltransferases, said Li. The group hope to develop their work in part by looking more closely at the sialylation effects of a specific sialyltransferase inhibitor on a branched glycoconjugate involved in regulation of immune response.

'This approach provides a simple way to the design of new and optimal sialyltransferase inhibitors (or prodrugs) for clinical investigation,' said Li.

Katherine Davies


K-H. Chang et al., Chem. Commun., 2006, 629  (DOI: 10.1039/b514915k)