title: Mixing of peptides and electrophilic traps gives rise to potent, broad-spectrum proteasome inhibitors.
abstract: The synthesis and evaluation of hybrid proteasome inhibitors that contain structural elements of the known inhibitors bortezomib, epoxomicin and peptide vinyl sulfones is described. From the panel of 15 inhibitors some structure activity relationships can be deduced with regard to inhibitory activity in relation to peptide recognition element, inhibitor size and nature of the electrophilic trap. Further, the panel contains one of the most potent peptide-based pan-proteasome inhibitors reported to date.
authors.affiliation: Bio-organic synthesis, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Verdoes
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Florea
authors.forename: Wouter A
authors.initials: WA
authors.lastname: van der Linden
authors.forename: Didier
authors.initials: D
authors.lastname: Renou
authors.forename: Adrianus M C H
authors.initials: AM
authors.lastname: van den Nieuwendijk
authors.forename: Gijs A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
mesh_terms: D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex