1. Peptidyl succinimidyl peptides as taspase 1 inhibitors.
- Author
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van den Boom J, Mamić M, Baccelliere D, Zweerink S, Kaschani F, Knauer S, Bayer P, and Kaiser M
- Subjects
- Dose-Response Relationship, Drug, Humans, Molecular Conformation, Peptides chemical synthesis, Peptides chemistry, Protease Inhibitors chemical synthesis, Protease Inhibitors chemistry, Structure-Activity Relationship, Endopeptidases metabolism, Peptides pharmacology, Protease Inhibitors pharmacology
- 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., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2014
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