Chemical synthesis of on demand-activated SUMO-based probe by a photocaged glycine-assisted strategy

Bioorg Med Chem Lett. 2023 Oct 1:94:129460. doi: 10.1016/j.bmcl.2023.129460. Epub 2023 Aug 26.

Abstract

The transiently-activated SUMO probes are conducive to understand the dynamic control of SENPs activity. Here, we developed a photocaged glycine-assisted strategy for the construction of on demand-activated SUMO-ABPs. The light-sensitive groups installed at G92 and G64 backbone of SUMO-2 can temporarily block probes activity and hamper aspartimide formation, respectively, which enabled the efficient synthesis of inert SUMO-2 propargylamide (PA). The probe could be activated to capture SENPs upon photo-irradiation not only in vitro but also in intact cells, providing opportunities to further perform intracellular time-resolved proteome-wide profiling of SUMO-related enzymes.

Keywords: Activity-based SUMO probes; Photocaged glycine; Protein chemical synthesis; SUMOylation; Specific SUMO proteases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycine / chemistry
  • Molecular Probes* / chemistry
  • Molecular Probes* / metabolism
  • Photochemistry / methods
  • Pyruvates
  • SUMO-1 Protein* / chemistry
  • SUMO-1 Protein* / metabolism

Substances

  • Glycine
  • Pyruvates
  • sulfoenolpyruvate
  • SUMO-1 Protein
  • Molecular Probes