New cyclic peptide proteasome inhibitors.
Here we report the study of a new series of vinyl ester cyclopeptide analogues synthesized on the basis of our previous development of a class of cyclopeptides derived from our linear prototype inhibitors. In these compounds, the exocyclic pharmacophoric unit Leu-VE was linked to the gamma-carboxyl group of the glutamic acid residue at the C-terminal. The best analogues of the series have been shown to inhibit the caspase-like activity of the proteasome at nanomolar concentrations and have also demonstrated good resistance to proteolysis and a capacity to permeate the cell membrane.
Baldisserotto
Anna
A
Department of Pharmaceutical Sciences and Centre of Biotechnology, University of Ferrara, 44100 Ferrara, Italy.
Marastoni
Mauro
M
Gavioli
Riccardo
R
Tomatis
Roberto
R
D000595:Amino Acid Sequence; D002460:Cell Line; D006207:Half-Life; D006801:Humans; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000493:pharmacokinetics; D011480:Protease Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors
D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex