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Arecoline Tripeptide Inhibitors of Proteasome

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posted on 2004-03-11, 00:00 authored by Mauro Marastoni, Anna Baldisserotto, Alessandro Canella, Riccardo Gavioli, Carmela De Risi, Gian Piero Pollini, Roberto Tomatis
The 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 1719 are the best compounds of the series, showing chymotryptic-like (β5) inhibition (IC50 ≅ 1 μM) and favorable pharmacokinetic properties.

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