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

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journal contribution
posted on 2010-09-09, 00:00 authored 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.