Author:
Matulienė Jurgita,Žvinys Gediminas,Petrauskas Vytautas,Kvietkauskaitė Agnė,Zakšauskas Audrius,Shubin Kirill,Zubrienė Asta,Baranauskienė Lina,Kačenauskaitė Lina,Kopanchuk Sergei,Veiksina Santa,Paketurytė-Latvė Vaida,Smirnovienė Joana,Juozapaitienė Vaida,Mickevičiūtė Aurelija,Michailovienė Vilma,Jachno Jelena,Stravinskienė Dovilė,Sližienė Aistė,Petrošiūtė Agnė,Becker Holger M.,Kazokaitė-Adomaitienė Justina,Yaromina Ala,Čapkauskaitė Edita,Rinken Ago,Dudutienė Virginija,Dubois Ludwig J,Matulis Daumantas
Abstract
AbstractNumerous human cancers, especially hypoxic solid tumors, express carbonic anhydrase IX (CAIX), a transmembrane protein with its catalytic domain located in the extracellular space. CAIX acidifies the tumor microenvironment, promotes metastases and invasiveness, and is therefore considered a promising anticancer target. We have designed a series of high affinity and high selectivity fluorescein-labeled compounds targeting CAIX to visualize and quantify CAIX expression in cancer cells. The competitive binding model enabled the determination of common CA inhibitors’ dissociation constants for CAIX expressed in exponentially growing cancer cells. All tested sulfonamide compounds bound the proliferating cells with similar affinity as to recombinantly purified CAIX. The probes are applicable for the design of selective drug-like compounds for CAIX and the competition strategy could be applied to other drug targets.
Funder
Lietuvos Mokslo Taryba
Estonian Research Council
Publisher
Springer Science and Business Media LLC