Synthesis and characterization of L-3-(pentafluorophosphato-difluoromethyl)-alanine, a structural and functional mimetic of phosphoserine

Abstract

Serine phosphorylation is an essential switch for regulating the interactions and functions of many disease-related proteins. Accordingly, stable phosphoserine mimetics constitute chemical tools to study the effects of these post-translational modifications. In this work, we present the synthesis and characterization of a novel structural analog of phosphoserine, L-3-(pentafluorophosphato-difluoromethyl)-alanine. The hyper-fluorinated amino acid was synthetically accessed in six steps starting from commercially available N-Boc-L-serine methyl ester. The protected PF₅ amino acid and peptides derived thereof were inhibitors of the serine protein phosphatase PPP2CA, demonstrating its activity as functional phosphoserine mimetic.