A suicide inhibitor of nematode trehalose-6-phosphate phosphatases
Megan Cross, Mark York, Ewa Dlugosz, Jan Hendrik Straub, Sonja Biberacher, HMP Dilrukshi Herath, Stephanie A Logan, Jeong-Sun Kim, Robin B Gasser, John H Ryan, Andreas Hofmann
SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2019
Protein-based drug discovery strategies have the distinct advantage of providing insights into the molecular mechanisms of chemical effectors. Currently, there are no known trehalose-6-phosphate phosphatase (TPP) inhibitors that possess reasonable inhibition constants and chemical scaffolds amenable to convenient modification. In the present study, we subjected recombinant TPPs to a two-tiered screening approach to evaluate several diverse compound groups with respect to their potential as TPP inhibitors. From a total of 5452 compounds tested, N-(phenylthio)phthalimide was identified as an inhibitor of nematode TPPs with apparent Ki values of 1.0 μM and 0.56 μM against the enzymes from the z..View full abstract
MC was supported by an Equity Trustees PhD Scholarship as well as an Australian Government Research Training Program Scholarship. JHS was recipient of a DAAD RISE and SB of a DAAD PROMOS scholarship. Research in the investigators' laboratories is funded by the Australian Research Council (AH and RBG) and the Rebecca L. Cooper Medical Research Foundation (AH). Aspects of this research have been facilitated by access to the Australian Proteome Analysis Facility supported under the Australian Government's National Collaborative Research Infrastructure Strategy (NCRIS).