jm0309102_si_001.pdf (89.18 kB)
Arecoline Tripeptide Inhibitors of Proteasome
journal contribution
posted on 2004-03-11, 00:00 authored by Mauro Marastoni, Anna Baldisserotto, Alessandro Canella, Riccardo Gavioli, Carmela De Risi, Gian Piero Pollini, Roberto TomatisThe 26S proteasome is a multicatalytic protease complex that plays an essential role in
intracellular protein degradation. We have synthesized and tested a series of arecoline peptide
derivatives where the peptide portion derives from a screening of tripeptide sequences, and
the arecoline moiety has been considered as a potential substrate for catalytic threonine.
Derivatives 17−19 are the best compounds of the series, showing chymotryptic-like (β5)
inhibition (IC50 ≅ 1 μM) and favorable pharmacokinetic properties.