title: Peptidomimetics containing a vinyl ketone warhead as falcipain-2 inhibitors.
abstract: The design, chemical synthesis, and enzymatic activity evaluation of a set of falcipain-2 inhibitors are reported. These compounds contain a proven peptidomimetic recognition motif based on a benzo[1,4]diazepin-2-one (1,4-BDZ) framework built on a dipeptide sequence, and a Michael acceptor terminal moiety capable of deactivating the cysteine protease active site. Our goal is to modify the P(3) site of this motif in order to identify the structural requirements for the interaction with the target.
authors.affiliation: Dipartimento Farmaco-Chimico, University of Messina, Viale Annunziata, 98168 Messina, Italy. rettari@pharma.unime.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Ettari
authors.forename: Maria
authors.initials: M
authors.lastname: Zappalà
authors.forename: Nicola
authors.initials: N
authors.lastname: Micale
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grazioso
authors.forename: Salvatore
authors.initials: S
authors.lastname: Giofrè
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.forename: Silvana
authors.initials: S
authors.lastname: Grasso
mesh_terms: D001570:Benzodiazepinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D057786:Peptidomimetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001570:Benzodiazepinones; D015853:Cysteine Proteinase Inhibitors; D057786:Peptidomimetics; C557005:benzo(1,4)diazepin-2-one; D003546:Cysteine Endopeptidases; C416224:falcipain 2