The discovery that proteins and/or protein families of interest can be labelled selectively with chemical reagents resulted in an active research field that aims to profile the amount and activity of (a subset of) proteins in a relevant setting. For this purpose, a diverse set of so-called activity- and affinity-based probes (ABPs) have been developed nowadays. The molecular structure of these probes generally consists of a recognition element, which generates selectivity for the protein of interest, a reactive group or warhead, which facilitates covalent binding of the probe to the protein, and a reporter group, which is used for read-out purposes. The activity-based protein profiling field has matured over the past decades and these research tools are nowadays employed in both fundamental and applied settings.
During this webinar, I will introduce the basics of activity- and affinity-based protein profiling. I will describe the general design approaches for ABPs, as well as their applications. In the second part of the webinar, I will discuss novel combinatorial approaches to prepare probes and I will demonstrate how chemical probes can be combined with nanoLC-MS/MS and docking studies to map the binding sites of small molecules.