Structural characterization of P1 '-diversified urea-based inhibitors of glutamate carboxypeptidase II

0433586 - BTÚ 2015 RIV GB eng J - Článek v odborném periodiku
Pavlíček, Jiří - Ptáček, Jakub - Černý, Jiří - Byun, Y. - Škultétyová, Ĺubica - Pomper, M.G. - Lubkowski, J. - Bařinka, Cyril
Structural characterization of P1 '-diversified urea-based inhibitors of glutamate carboxypeptidase II.
Bioorganic and Medicinal Chemistry Letters. Roč. 24, č. 10 (2014), s. 2340-2345. ISSN 0960-894X. E-ISSN 1464-3405
Grant CEP: GA MŠMT(CZ) ED1.1.00/02.0109
Grant ostatní: EMBO(DE) 1978
Institucionální podpora: RVO:86652036
Klíčová slova: GCPII * Prostate-specific membrane antigen * PSMA
Kód oboru RIV: FR - Farmakologie a lékárnická chemie
Impakt faktor: 2.420, rok: 2014

Urea-based inhibitors of human glutamate carboxypeptidase II (GCPII) have advanced into clinical trials for imaging metastatic prostate cancer. In parallel efforts, agents with increased lipophilicity have been designed and evaluated for targeting GCPII residing within the neuraxis. Here we report the structural and computational characterization of six complexes between GCPII and P1 '-diversified urea-based inhibitors that have the C-terminal glutamate replaced by more hydrophobic moieties. The X-ray structures are complemented by quantum mechanics calculations that provide a quantitative insight into the GCPII/inhibitor interactions. These data can be used for the rational design of novel glutamate-free GCPII inhibitors with tailored physicochemical properties. (C) 2014 Elsevier Ltd. All rights reserved.
Trvalý link: http://hdl.handle.net/11104/0238115