title: Synthesis and proteasome inhibition of N-allyl vinyl ester-based peptides.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, I 44100 Ferrara, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Baldisserotto
authors.forename: Christian
authors.initials: C
authors.lastname: Franceschini
authors.forename: Franco
authors.initials: F
authors.lastname: Scalambra
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.forename: Mauro
authors.initials: M
authors.lastname: Marastoni
authors.forename: Fabio
authors.initials: F
authors.lastname: Sforza
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gavioli
authors.forename: Roberto
authors.initials: R
authors.lastname: Tomatis
mesh_terms: 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
chemical_list: D000498:Allyl Compounds; D009842:Oligopeptides; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors