Synthesis and biological evaluation of pentafluorophosphates as amphiphilic non-cleavable phosphatase inhibitors

Abstract

The aim of this work was the identification and the subsequent fine tuning of a convenient synthetic route from commercially available phenylalanine to pentafluorophosphates, as well as the incorporation of these fluorine-rich, amphiphilic phosphotyrosine mimetics in peptides. Although acid sensibility of pentafluorophosphates hampered the identification of a protocol compatible with solid phase peptide synthesis (SPPS), this was ultimately achieved using an excess of fluorides that allowed the synthesis of mono and bivalent model peptides. After the synthesis on solid support, the determination of the inhibitory potential against protein tyrosine phosphatase 1B (PTP1B) was determined in a photometric assay. Furthermore, in a joint research work it was possible to further investigate properties and potential of this moiety, including the crystal structure and the lipophilicity of the first pentafluorinated amino acid.