title: C-terminal trans,trans-muconic acid ethyl ester partial retro-inverso pseudopeptides as proteasome inhibitors.
abstract: The development of specific inhibitors of the proteasome represents an important opportunity for new drug therapies. The central role of the multicatalytic complex in the intracellular proteolysis mediated by ubiquitin-proteasome pathway goes to discovery many molecules able to selectively inhibits enzymatic active subsites. Now, we report synthesis and activity of a new partial retro-inverso oligopseudopeptide derivatives bearing a trans,trans-muconic acid ethyl ester pharmacophoric unit at the C-terminal. Some analogues selectively inhibited in µM range the caspase-like (C-L) activity in the β1 subunit 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: Rosaria
authors.initials: R
authors.lastname: Calia
authors.forename: Alessandra
authors.initials: A
authors.lastname: Scotti
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: D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013011:Sorbic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004952:Esters; D010455:Peptides; D061988:Proteasome Inhibitors; C005939:muconic acid; D046988:Proteasome Endopeptidase Complex; D013011:Sorbic Acid