Development of lipopeptides for inhibiting 20S proteasomes.

Nicolas Basse, David Papapostolou, Maurice Pagano, Michèle Reboud-Ravaux, Elise Bernard, Anne-Sophie Felten, Régis Vanderesse

Index: Bioorg. Med. Chem. Lett. 16 , 3277-81, (2006)

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Abstract

Proteasomes are responsible for the cytoplasmic turnover of the vast majority of proteins including regulatory proteins. We have synthesized lipopeptides a new class of non-covalent inhibitors of the 20S proteasome and assayed their inhibitory capacities. Their ability to inhibit at micromolar concentrations chymotrypsin-like and post-acid activities depends on peptide length (3 or 6 amino acids), sequence (presence of a positively or negatively charged amino acid), and alkyl chain length (C6-C18). These structural features could be varied to selectively inhibit one or more of the three proteasome activities.