Identification of sialyltransferase inhibitors and their use in the development of a chemical genetics tool for the study of normal and pathological cell surface carbohydrate modification

The complex arrangement of carbohydrates that cover the surfaces of cells is known to play a key role in biological processes ranging from cellular recognition to gene regulation. Changes in the composition of these carbohydrate structures are linked to the onset of many diseases, including the proliferation of cancer cells and compromised immune function. Research suggests that these changes are often associated with elevated activities of the enzymes responsible for sugar placement. As such, these enzymes (glycosyltransferases) represent an attractive drug target for the treatment of many human diseases. Unfortunately, multiple enzyme forms for a given sugar transfer are encoded by the human genome and the role that individual genes play in both normal and pathological cell surface modification remains largely unknown. Luke Lairson’s goal is to identify the small molecules that inhibit the activity of a class of glycosyltransferases known as sialyltransferases. These enzymes are responsible for adding a particular type of sugar known as sialic acid (known to play a key role in many types of cancer) to cell surfaces. Luke hopes that identifying these small molecules will serve as a potential starting point for the development of a new class of anti-cancer drug. His results may also be used to develop a technology for the identification of individual gene products responsible for the placement of particular sugars in both normal and diseased cells at a given point during development.