title: Novel selective inhibitors of aminopeptidases that generate antigenic peptides.
abstract: Endoplasmic reticulum aminopeptidases, ERAP1 and ERAP2, as well as Insulin regulated aminopeptidase (IRAP) play key roles in antigen processing, and have recently emerged as biologically important targets for manipulation of antigen presentation. Taking advantage of the available structural and substrate-selectivity data for these enzymes, we have rationally designed a new series of inhibitors that display low micromolar activity. The selectivity profile for these three highly homologous aminopeptidases provides a promising avenue for modulating intracellular antigen processing.
authors.affiliation: Department of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papakyriakou
authors.forename: Efthalia
authors.initials: E
authors.lastname: Zervoudi
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Theodorakis
authors.forename: Loredana
authors.initials: L
authors.lastname: Saveanu
authors.forename: Efstratios
authors.initials: E
authors.lastname: Stratikos
authors.forename: Dionisios
authors.initials: D
authors.lastname: Vourloumis
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D010122:Cystinyl Aminopeptidase / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular
chemical_list: D004791:Enzyme Inhibitors; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase
keywords: ERAP1; ERAP2; Endoplasmic reticulum aminopeptidase; IRAP; Molecular modeling; Rational design; Selective inhibitor