PhD defence: Development of Fluorinated Substrate-Based Inhibitors and Prodrugs for Fucosyltransferases and Sialyltransferases

PLEASE NOTE: If a candidate gives a layman's talk, the livestream will start fifteen minutes earlier.

This PhD project focuses on the development of new chemical tools to control enzymes that attach sugars to proteins and lipids on the surface of cells. These sugar structures play key roles in cell communication, immune responses, and tumour development. Changes in these processes are linked to various diseases, including cancer.

The research specifically targets two groups of enzymes: fucosyltransferases and sialyltransferases. Existing inhibitors of these enzymes often have important limitations, such as slow activity or unwanted incorporation into cellular sugar structures. In this thesis, new fluorine-containing sugar analogues were designed to overcome these drawbacks and to allow more precise control over enzyme activity.

One major outcome of this work is the development of improved inhibitors for fucosyltransferases that effectively reduce sugar modification on the cell surface without being incorporated into cellular structures themselves. This enables controlled regulation of sugar levels in cells. In addition, new molecules were explored that can selectively inhibit specific sialyltransferases, which is important because different enzymes perform distinct functions in healthy and diseased cells.

Although not all compounds showed strong activity in living cells, this research provides valuable insights into how cellular sugar modifications can be chemically manipulated. These findings lay an important foundation for the future development of selective research tools and potential therapeutic strategies aimed at understanding and influencing disease-related changes in cell-surface sugars.