This dissertation entitled “Exploring the Ub/Ubl landscape with activity-based probes” describes the development of chemical tools to probe the reactivity of the Ubiquitin/Ubiquitin-like enzymatic cascade. Initially, the incorporation of an unnatural amino acid into proteins to enable covalent-substrate capture was attempted and continued with the development of the innovate cascading Ubiquitin probe capable of sequentially targeting Ubiquitin activating, conjugating, and ligating enzymes. Later, the improvement of peptide synthesis methods enabled the generation of a SUMO and UFM1 activity-based probes. Although the introduction of an activity-based probe for UFM1—an understudied Ubiquitin-like modifier—facilitates the study of its conjugating and deconjugating enzymes, the underlying biology of UFMylation remains elusive. To address this unmet need, a proteomics approach to identify UFMylated substrates and validation of one of its primary targets were undertaken.
Katharina F. Witting defended her thesis entitled 'Exploring the Ub/Ubl landscape with activity-based probes ' and succeeded in doing so with distinction (cum laude).
Date: May 20th, 2020