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α,β-Unsaturated N-Acylpyrrole Peptidyl Derivatives: New Proteasome Inhibitors

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journal contribution
posted on 09.09.2010 by Anna Baldisserotto, Valeria Ferretti, Federica Destro, Christian Franceschini, Mauro Marastoni, Riccardo Gavioli, Roberto Tomatis
Because of the encouraging results obtained using vinyl ester derivatives, we synthesized and tested a novel series of peptide-based proteasome inhibitors bearing a new pharmacophore unit at the C-terminal. N-Acylpyrrole moiety is a potential substrate for Michael addition by catalytic threonine. Several analogues have demonstrated a selective inhibition of the multicatalytic complex β1 subunits, the capacity to permeate cellular membrane, and good pharmacokinetics properties.