Details

Autor(en) / Beteiligte

• Baldisserotto, Anna
• Destro, Federica
• Vertuani, Gianni
• Marastoni, Mauro
• Gavioli, Riccardo
• Tomatis, Roberto

Titel

N-terminal-prolonged vinyl ester-based peptides as selective proteasome beta1 subunit inhibitors

Ist Teil von

• Bioorganic & medicinal chemistry, 2009-08, Vol.17 (15), p.5535-5540

Ort / Verlag

England

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• The synthesis and biological properties of vinyl ester peptide-based molecules bearing linear N-terminal amino acids are reported. Compounds were tested in vitro for their capacity to inhibit the chymotryptic-, tryptic-like, and post-acidic activities of the proteasome. Some analogues showed selective inhibition of post-acidic (PGPH) activity, which is attributed to the beta1 subunit. Interestingly, active compounds demonstrated higher inhibitory activity toward 'standard' proteasomes than toward immunoproteasomes. The inhibitory potency was found to be related to the amino acidic sequence and to the length of the N-terminal residues. The new inhibitors demonstrated resistance to plasmatic proteases and a good capacity to permeate the cell membrane.