Herman Overkleeft is an organic chemist and chemical biologist whose activity-based protein profiling (ABPP) program (Acc Chem Res 2011, 718) is recognized as leading internationally. His lab was the first (coinciding with the Cravatt group) to connect ABPP with bioorthogonal chemistry (van Swieten, Angew Chem Int Ed 2003) and the first to perform three bioorthogonal reactions in a single experiment (Willems, Angew Chem Int Ed 2012). His lab developed a chemoselective linker for chemical proteomics profiling (Geurink, Angew Chem Int Ed, 2009), and lysosomal cysteine protease (cathepsin) ABPs targeted to cells through the mannose receptor (Hillaert, Angew Chem Int Ed, 2010) and the M6P receptor (Hoogendoorn, Angew Chem Int Ed, 2014). The developed inhibitors and activity-based probes are highly sought-after commodities both for application in biomedicine and biotechnology studies. This has led to numerous fruitful collaborations, and to weekly shipments of compounds without strings attached to interested colleagues.

A main focus throughout the years has been the development of inhibitors and activity-based probes for human constitutive proteasomes and immunoproteasomes. This has resulted in a unique set of reagents and tools with which each of the six catalytic activities of the human constitutive proteasome and immunoproteasome combined can be inhibited and visualized (van Swieten, Angew Chem Int Ed 2003; de Bruin, Angew Chem Int Ed 2016; de Bruin, J Am Chem Soc 2016). Key collaborators on proteasome research are Alexei Kisselev (Auburn University, Alabama, USA; biochemistry, enzymology), Michael Groll (Technical University Munich, Germany; enzymology, structural biology) and Christoph Driessen (St Gallen Medical Centre, Switzerland; onco-haematology).