Design of Highly Potent Urea-Based, Exosite-Binding Inhibitors Selective for Glutamate Carboxypeptidase II

0445391 - ÚOCHB 2016 RIV US eng J - Journal Article
Tykvart, Jan - Schimer, Jiří - Jančařík, Andrej - Bařinková, Jitka - Navrátil, Václav - Starková, Jana - Šrámková, Karolína - Konvalinka, Jan - Majer, Pavel - Šácha, Pavel
Design of Highly Potent Urea-Based, Exosite-Binding Inhibitors Selective for Glutamate Carboxypeptidase II.
Journal of Medicinal Chemistry. Roč. 58, č. 10 (2015), s. 4357-4363. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA ČR GBP208/12/G016; GA MŠMT LO1302
Institutional support: RVO:61388963
Keywords : GCPII selective inhibitors * GCPIII * GCPII
Subject RIV: CE - Biochemistry
Impact factor: 5.589, year: 2015

We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active toward, GCPII than its closest human homologue, glutamate carboxypeptidase III (GCPIII). Additionally, we demonstrate that the prepared inhibitor conjugate can be used for sensitive and selective imaging of GCPII in mammalian cells.
Permanent Link: http://hdl.handle.net/11104/0247685