Strategies for Tuning the Selectivity of Chemical Probes that Target Serine Hydrolases

Franco Faucher, John M Bennett, Matthew Bogyo, Scott Lovell

Research output: Contribution to journalReview articlepeer-review

30 Citations (SciVal)


Serine hydrolases comprise a large family of enzymes that have diverse roles in key cellular processes, such as lipid metabolism, cell signaling, and regulation of post-translation modifications of proteins. They are also therapeutic targets for multiple human pathologies, including viral infection, diabetes, hypertension, and Alzheimer disease; however, few have well-defined substrates and biological functions. Activity-based probes (ABPs) have been used as effective tools to both profile activity and screen for selective inhibitors of serine hydrolases. One broad-spectrum ABP containing a fluorophosphonate electrophile has been used extensively to advance our understanding of diverse serine hydrolases. Due to the success of this single reagent, several robust chemistries have been developed to further diversify and tune the selectivity of ABPs used to target serine hydrolases. In this review, we highlight approaches to identify selective serine hydrolase ABPs and suggest new synthetic methodologies that could be applied to further advance probe development.

Original languageEnglish
Pages (from-to)937-952
Number of pages16
JournalCell Chemical Biology
Issue number8
Early online date20 Aug 2020
Publication statusPublished - 20 Aug 2020


  • Click Chemistry
  • Fluorescent Dyes/chemistry
  • Organophosphonates/chemistry
  • Peptides/chemistry
  • Proteomics
  • Rhodamines/chemistry
  • Serine Proteases/chemistry
  • Small Molecule Libraries/chemistry


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