title: Peptidomimetics as protein arginine deiminase 4 (PAD4) inhibitors.
abstract: The protein arginine deiminase 4 (PAD4) is a calcium-dependent enzyme, which catalyses the irreversible conversion of peptidyl-arginines into peptidyl-citrullines and plays an important role in several diseases such as in the rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Creutzfeldt-Jacob's disease and cancer. In this study, we report the inhibition profiles and computational docking toward the PAD4 enzyme of a series of 1,2,3-triazole peptidomimetic-based derivatives incorporating the β-phenylalanine and guanidine scaffolds. Several effective, low micromolar PAD4 inhibitors are reported in this study.
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence , Sesto Fiorentino, Florence , Italy .
authors.forename: Andrea
authors.initials: A
authors.lastname: Trabocchi
authors.forename: Nicolino
authors.initials: N
authors.lastname: Pala
authors.forename: Ilga
authors.initials: I
authors.lastname: Krimmelbein
authors.forename: Gloria
authors.initials: G
authors.lastname: Menchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Guarna
authors.forename: Mario
authors.initials: M
authors.lastname: Sechi
authors.forename: Tobias
authors.initials: T
authors.lastname: Dreker
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D057786:Peptidomimetics; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
keywords: Arginine mimic; PAD4 inhibitors; cancer; peptidomimetic; rheumatoid arthritis