A cell-permeable, peptide vinyl sulfone that acts as a potent, irreversible inhibitor of proteasome activity. Covalently modifies the catalytically active β-subunits of the proteasome. Shown to inhibit the chymotrypsin-like (10-50 nM), trypsin-like (1-5 µM), and the peptidyl glutamyl peptide hydrolyzing (PGPH) (0.5-1 µM) activities of purified 20S proteasomes from rabbit muscle. Inhibits proteasomal degradation of deglycosylated MHC HLA-A2 heavy chain in US11+ cells (~50 µM).