P3 and P4 position analysis of vinyl ester pseudopeptide proteasome inhibitors

Two small libraries of tripeptidic-based vinyl ester derivative proteasome inhibitors were synthesized and tested, starting with the Hmb-Val-Gln-Leu-VE prototype. The P3 and P4 positions were investigated with a complete set of amino acid residues, some of which showed remarkable selective inhibition of the trypsin-like (β2) subunit. In both positions, aromatic and hydrophobic residues were preferred.

Graphical abstractHere following is the report on the use of small, focused libraries to study P3 and P4 positions of vinyl ester pseudopeptides, selective inhibitors for trypsin-like activity of the 20S proteasome.Figure optionsDownload full-size imageDownload as PowerPoint slide