Inhibitor-Polymer Conjugates as a Versatile Tool for Detection and Visualization of Cancer-Associated Carbonic Anhydrase Isoforms

0505496 - ÚOCHB 2020 RIV US eng J - Journal Article
Pospíšilová, Klára - Knedlík, Tomáš - Šácha, Pavel - Kostka, Libor - Schimer, Jiří - Brynda, Jiří - Král, V. - Cígler, Petr - Navrátil, Václav - Etrych, Tomáš - Šubr, Vladimír - Kugler, Michael - Fábry, M. - Řezáčová, Pavlína - Konvalinka, Jan
Inhibitor-Polymer Conjugates as a Versatile Tool for Detection and Visualization of Cancer-Associated Carbonic Anhydrase Isoforms.
ACS Omega. Roč. 4, č. 4 (2019), s. 6746-6756. ISSN 2470-1343. E-ISSN 2470-1343
R&D Projects: GA ČR(CZ) GA16-02938S; GA MŠMT(CZ) LO1304; GA MŠMT LO1302; GA MŠMT(CZ) EF16_019/0000729; GA MŠMT EF16_026/0008382
Institutional support: RVO:61388963 ; RVO:61389013
Keywords : renal-cell carcinoma * molecule-drug conjugate * intrinsic marker
OECD category: Biochemistry and molecular biology; Polymer science (UMCH-V)
Impact factor: 2.870, year: 2019
Method of publishing: Open access
https://pubs.acs.org/doi/10.1021/acsomega.9b00596

Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze hydration of carbon dioxide to bicarbonate. They play a crucial role in a number of important physiological processes. CAIX is a tumor-associated transmembrane isoenzyme that is overexpressed on the cell surface in hypoxic solid tumors and represents a validated target for cancer therapy and diagnosis. Here, we describe development of an N-(2-hydroxypropyl)methacrylamide-based copolymer conjugate (iBody) containing a CAIX inhibitor for selective targeting of this enzyme on tumor cells. The iBody binds CAIX with sufficient affinity for use in biochemical applications. We show that the iBody can be used to isolate CAIX from cell lysates and to visualize it by flow cytometry and confocal microscopy. Our results demonstrate that the iBody is a valuable tool for targeting CAIX in vitro and with further development may serve as a platform for CAIX targeting in vivo.
Permanent Link: http://hdl.handle.net/11104/0296982