Total Chemical Synthesis of SUMO and SUMO‐Based Probes for Profiling the Activity of SUMO‐Specific Proteases
Copyright policy )Total Chemical Synthesis of SUMO and SUMO‐Based Probes for Profiling the Activity of SUMO‐Specific Proteases
AbstractSUMO is a post‐translational modifier critical for cell cycle progression and genome stability that plays a role in tumorigenesis, thus rendering SUMO‐specific enzymes potential pharmacological targets. However, the systematic generation of tools for the activity profiling of SUMO‐specific enzymes has proven challenging. We developed a diversifiable synthetic platform for SUMO‐based probes by using a direct linear synthesis method, which permits N‐ and C‐terminal labelling to incorporate dyes and reactive warheads, respectively. In this manner, activity‐based probes (ABPs) for SUMO‐1, SUMO‐2, and SUMO‐3‐specific proteases were generated and validated in cells using gel‐based assays and confocal microscopy. We further expanded our toolbox with the synthesis of a K11‐linked diSUMO‐2 probe to study the proteolytic cleavage of SUMO chains. Together, these ABPs demonstrate the versatility and specificity of our synthetic SUMO platform for in vitro and in vivo characterization of the SUMO protease family.
- Leiden University Netherlands
- Leiden University Netherlands
- Oncode Institute Netherlands
- Antoni van Leeuwenhoek Hospital Netherlands
- Leiden University Netherlands
Models, Molecular, proteolysis, Microscopy, Confocal, Communications, Substrate Specificity, Microscopy, Fluorescence, SUMO, solid-phase peptide synthesis, Proteolysis, post-translational modifications, Small Ubiquitin-Related Modifier Proteins, Humans, Peptides, Solid-Phase Synthesis Techniques, activity-based protein profiling, HeLa Cells, Peptide Hydrolases
Models, Molecular, proteolysis, Microscopy, Confocal, Communications, Substrate Specificity, Microscopy, Fluorescence, SUMO, solid-phase peptide synthesis, Proteolysis, post-translational modifications, Small Ubiquitin-Related Modifier Proteins, Humans, Peptides, Solid-Phase Synthesis Techniques, activity-based protein profiling, HeLa Cells, Peptide Hydrolases
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