title: C-terminal constrained phenylalanine as a pharmacophoric unit in peptide-based proteasome inhibitors.
abstract: Here we report the synthesis and biological properties of peptide-based molecules bearing constrained analogues of phenylalanine at the C-terminal. Compounds were tested as proteasome subunits' inhibitors. Dehydro-peptides showed good inhibition, in particular against trypsin-like (T-L) proteasome activity while some C-terminal Tic-derivatives inhibit only caspase-like activity in enzymatic beta1 subunits with a certain degree of efficacy. The best analogues of the series demonstrated good resistance to proteolysis and a capacity to permeate the cell membrane.
authors.affiliation: Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, Ferrara, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Baldisserotto
authors.forename: Mauro
authors.initials: M
authors.lastname: Marastoni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lazzari
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gavioli
authors.forename: Roberto
authors.initials: R
authors.lastname: Tomatis
mesh_terms: D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004795:Enzyme Stability; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010649:Phenylalanine / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors
chemical_list: D015853:Cysteine Proteinase Inhibitors; D061988:Proteasome Inhibitors; D010649:Phenylalanine; D046988:Proteasome Endopeptidase Complex