A5066813728- Ubiquitin and proteasome pathways
- 14-3-3 protein interactions
- Hippo pathway signaling and YAP/TAZ
- Biochemical and Structural Characterization
- Microbial Natural Products and Biosynthesis
- Heat shock proteins research
Eindhoven University of Technology
2020-2024
Lead Discovery Center (Germany)
2020-2024
DNA-encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain tryptophan plays a prominent role in key, or "hot spot", regions protein-protein interactions. A peptoid library was designed based on the Ugi four-component reaction by employing tryptophan-mimetic chains to probe surface target proteins. Several peptoids were synthesized chemically stable hexathymidine adapter oligonucleotide "hexT",...
The identification of chemical starting points for the development molecular glues is challenging. Here, we employed fragment screening and identified an allosteric stabilizer complex between 14–3–3 a TAZ-derived peptide. binds preferentially to 14–3–3/TAZ peptide shows moderate stabilization in differential scanning fluorimetry microscale thermophoresis. binding site was predicted by dynamics calculations be distant from interface, located helices 8 9 protein. This confirmed nuclear...
Abstract DNA‐encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain tryptophan plays a prominent role in key, or “hot spot”, regions protein–protein interactions. A peptoid library was designed based on the Ugi four‐component reaction by employing tryptophan‐mimetic chains to probe surface target proteins. Several peptoids were synthesized chemically stable hexathymidine adapter oligonucleotide...
The modulation of protein-protein interactions (PPIs) has developed into a well-established field drug discovery. Despite the advances achieved in field, many PPIs are still deemed as 'undruggable' targets and design stabilizers remains significant challenge. application fragment-based methods for identification leads to evaluate 'tractability' desired protein target seen remarkable development recent years. In this study, we explore molecular characteristics 14-3-3/Amot-p130 PPI conceptual...
The Hippo pathway plays an important role in organ size control and tissue homeostasis. Dysregulation is involved many pathologies, including cancer, which has attracted interest targeting the pathway. Since upstream components are bona fide tumor suppressors, it feasible to target oncogenic downstream targets such as TAZ, a key effector Its activity regulated by phosphorylation on multiple sites, with Ser89 playing critical regulation of TAZ activity. Phosphorylation at promotes binding...