Immunoproteasome β5i-Selective Dipeptidomimetic Inhibitors

N,C-capped dipeptides belong to a class of noncovalent proteasome inhibitors. Herein we report that the insertion of a β-amino acid into N,C-capped dipeptides markedly decreases their inhibitory potency against human constitutive proteasome β5c, while maintaining potent inhibitory activity against human immunoproteasome β5i, thereby achieving thousands-fold selectivity for β5i over β5c. Structure–activity relationship studies revealed that β5c...