title: Peptidyl succinimidyl peptides as taspase 1 inhibitors.
abstract: Taspase 1 is an N-terminal threonine protease implicated in leukemia and other cancers. Despite intensive efforts in recent years, only a limited number of Taspase 1 inhibitors are currently available, and they lack general applicability. Here we present a novel class of Taspase 1 inhibitors based on a peptidyl succinimidyl peptide motif. These inhibitors were obtained from the substrate cleavage sequence and mechanistic considerations involving the previously proposed asparaginase-type cleavage mechanism. We anticipate that this class of Taspase 1 inhibitor will find wide application in further biochemical and structural studies, for example for better investigating the molecular details of the unusual enzymatic cleavage mechanism of Taspase 1.
authors.affiliation: Strukturelle Biochemie, Universität Duisburg-Essen, Zentrum für Medizinische Biotechnologie, Universitätsstrasse 2, 45117 Essen (Germany).
authors.forename: Johannes
authors.initials: J
authors.lastname: van den Boom
authors.forename: Marija
authors.initials: M
authors.lastname: Mamić
authors.forename: Daniele
authors.initials: D
authors.lastname: Baccelliere
authors.forename: Susanne
authors.initials: S
authors.lastname: Zweerink
authors.forename: Farnusch
authors.initials: F
authors.lastname: Kaschani
authors.forename: Shirley
authors.initials: S
authors.lastname: Knauer
authors.forename: Peter
authors.initials: P
authors.lastname: Bayer
authors.forename: Markus
authors.initials: M
authors.lastname: Kaiser
mesh_terms: D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D011480:Protease Inhibitors; D010450:Endopeptidases; C480823:taspase1, human
keywords: Taspase; activity-based profiling; cancer; inhibitors; mechanism-based design; protease