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Peptidyl Succinimidyl Peptides as Taspase 1 Inhibitors
Author(s) -
van den Boom Johannes,
Mamić Marija,
Baccelliere Daniele,
Zweerink Susanne,
Kaschani Farnusch,
Knauer Shirley,
Bayer Peter,
Kaiser Markus
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402108
Subject(s) - cleavage (geology) , peptide , chemistry , protease , substrate specificity , biochemistry , enzyme , computational biology , stereochemistry , biology , combinatorial chemistry , paleontology , fracture (geology)
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.