Synthesis and proteasome inhibition of N-allyl vinyl ester-based peptides.
Inhibition of the proteasome, the multicatalytic protease complex responsible for the turnover of many cellular proteins, represents an attractive target in the development of new drug therapies, proteasome inhibitors being potentially useful tools for the treatment of pathologies such as cancer, as well as inflammatory, immune and neurodegenerative diseases. Based on our previous development of a new class of inhibitors bearing a C-terminal VE cluster able to interact with catalytic threonine, we report herein the synthesis and activity of new VE-based peptide analogs bearing an additional allyl pharmacophore unit at the C- or N-terminal position of the pseudotripeptide sequence. In the new series, the structural modification carried out to the prototype determine a decrease of proteasome inhibition.
Baldisserotto
Anna
A
Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, I 44100 Ferrara, Italy.
Franceschini
Christian
C
Scalambra
Franco
F
Trapella
Claudio
C
Marastoni
Mauro
M
Sforza
Fabio
F
Gavioli
Riccardo
R
Tomatis
Roberto
R
D000498:Allyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship
D000498:Allyl Compounds; D009842:Oligopeptides; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors