Počet záznamů: 1

Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery

SYSNO ASEP	0431499
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery
Tvůrce(i)	Tykvart, Jan (UOCHB-X)_{RID, ORCID} Schimer, Jiří (UOCHB-X)_{RID, ORCID} Bařinková, Jitka (UOCHB-X) Pachl, Petr (UOCHB-X)_{RID, ORCID} Poštová Slavětínská, Lenka (UOCHB-X)_RID Majer, Pavel (UOCHB-X) Konvalinka, Jan (UOCHB-X)_{RID, ORCID} Šácha, Pavel (UOCHB-X)_{RID, ORCID}
Celkový počet autorů	8
Zdroj.dok.	Bioorganic & Medicinal Chemistry. - : Elsevier - ISSN 0968-0896 Roč. 22, č. 15 (2014), s. 4099-4108
Poč.str.	10 s.
Jazyk dok.	eng - angličtina
Země vyd.	GB - Velká Británie
Klíč. slova	GCPII ; PSMA ; structure-aided drug design ; specific drug targeting
Vědní obor RIV	CE - Biochemie
CEP	GBP208/12/G016 GA ČR - Grantová agentura ČR
Institucionální podpora	UOCHB-X - RVO:61388963
UT WOS	000339859700034
EID SCOPUS	84905081813
DOI	10.1016/j.bmc.2014.05.061
Anotace	Glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), is an established prostate cancer marker and is considered a promising target for specific anticancer drug delivery. Low-molecular-weight inhibitors of GCPII are advantageous specific ligands for this purpose. However, they must be modified with a linker to enable connection of the ligand with an imaging molecule, anticancer drug, and/or nanocarrier. Here, we describe a structure-activity relationship (SAR) study of GCPII inhibitors with linkers suitable for imaging and drug delivery. Structure-assisted inhibitor design and targeting of a specific GCPII exosite resulted in a 7-fold improvement in K-i value compared to the parent structure. X-ray structural analysis of the inhibitor series led to the identification of several inhibitor binding modes. We also optimized the length of the inhibitor linker for effective attachment to a biotin-binding molecule and showed that the optimized inhibitor could be used to target nanoparticles to cells expressing GCPII.
Pracoviště	Ústav organické chemie a biochemie
Kontakt	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Rok sběru	2015

Počet záznamů: 1