Activity- & Affinity-Based Phospholipase Profiling: The Design, Synthesis and Biological Evaluation of Phospholipase-Targeting Activity- and Affinity-Based Probes and Inhibitors

Although a variety of different phospholipases was discovered in the past, I am convinced the family of phospholipases is still growing. Also, there is still a lot that could be learned from the types that were already identified, and for this reason the development of chemical probes that can both selectively and with high affinity bind members of the phospholipase family was and is a necessity. When I started my PhD trajectory in the end of 2017, I envisioned ‘filling up the chemical toolbox’ with new affinity- and activity-based probes (AfBPs & ABPs), thereby ‘completing’ the toolbox for phospholipases. While I am writing this, I realize that I (slightly) underestimated the size of the phospholipase family, and also the challenges arising when pursuing the development of both selective and high affinity chemical probes. Nevertheless, after all these years I am happy to present the design, synthesis and biological evaluation of nine new compounds in my PhD thesis.