Fluorophosphonate-Based Degrader Identifies Degradable Serine Hydrolases by Quantitative Proteomics

Chembiochem. 2020 Oct 15;21(20):2916-2920. doi: 10.1002/cbic.202000253. Epub 2020 Jul 23.

Abstract

Novel chemical biology probes linking a serine hydrolase-directed fluorophosphonate warhead and cereblon-binding pomalidomide were assessed for the degradation of serine hydrolases. A quantitative proteomics approach to detect degraded proteins revealed that, despite the engagement of ∼40 serine hydrolases, degradation was achieved for only a single serine hydrolase, lysophospholipase II (LYPLA2).

Keywords: LYPLA2; PROTAC; bioorganic chemistry; cereblon; proteomics.

MeSH terms

  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism
  • Hydrolases / analysis*
  • Hydrolases / metabolism
  • Molecular Structure
  • Phosphates / chemistry*
  • Phosphates / metabolism
  • Proteomics*
  • Serine / analysis*
  • Serine / metabolism
  • Thalidomide / analogs & derivatives*
  • Thalidomide / chemistry
  • Thalidomide / metabolism

Substances

  • Fluorescent Dyes
  • Phosphates
  • Serine
  • Thalidomide
  • pomalidomide
  • Hydrolases