title: Subtype-selectivity of metal-dependent methionine aminopeptidase inhibitors.
abstract: Inhibitors of methionine aminopeptidases (MetAPs) are treatment options for various pathological conditions. Several inhibitor classes have been described previously, but only few data on the subtype selectivity, which is of crucial importance for these enzymes, is available. We present a systematic study on the subtype- and species-selectivity of MetAP inhibitors that require the binding of an auxiliary metal ion. This includes, in particular, compounds based on the benzimidazole pharmacophore, but also hydroxyquinoline and picolinic acid derivatives. Our data indicates that a significant degree of selectivity can be attained with metal-dependent MetAP inhibitors.
authors.affiliation: Department of Medicinal Chemistry, Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Altmeyer
authors.forename: Aline
authors.initials: A
authors.lastname: Marschner
authors.forename: Rolf
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Christian D
authors.initials: CD
authors.lastname: Klein
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D063208:Methionyl Aminopeptidases; D008958:Models, Molecular; D008968:Molecular Conformation; D011480:Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D008670:Metals; D011480:Protease Inhibitors; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases