title: Synthesis and biological properties of C-terminal vinyl ketone pseudotripeptides.
abstract: The ubiquitin-proteasome pathway responsible for the turnover of many cellular proteins represents an attractive target in the development of new drug therapies: In particular, modulation of the proteasome activity by specific inhibitors may represent a useful tool for the treatment of tumours. Here, we report synthesis and activity of a new series of oligopseudopeptide analogues bearing a vinyl ketone pharmacophoric unit at the C-terminal position. Some derivatives showed inhibition in the µM range of the trypsin-like (T-L) active site of the proteasome.
authors.affiliation: Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, Ferrara, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Franceschini
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.forename: Fabio
authors.initials: F
authors.lastname: Sforza
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gavioli
authors.forename: Mauro
authors.initials: M
authors.lastname: Marastoni
mesh_terms: D060326:Chemistry Techniques, Synthetic / Q000379:methods; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D007659:Ketones / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000378:metabolism
chemical_list: D007659:Ketones; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D014357:Trypsin; D046988:Proteasome Endopeptidase Complex