Esterase activity of carbonic anhydrases serves as surrogate for selecting antibodies blocking hydratase activity.

Autor: Uda NR; a Department of Biomedicine , University of Basel , Basel , Switzerland ., Seibert V; b 4-Antibody AG (Wholly-Owned Subsidiary of Agenus Inc., USA) , Basel , Switzerland ., Stenner-Liewen F; a Department of Biomedicine , University of Basel , Basel , Switzerland .; c Department Internal Medicine , University Hospital Basel , Basel , Switzerland ., Müller P; a Department of Biomedicine , University of Basel , Basel , Switzerland ., Herzig P; a Department of Biomedicine , University of Basel , Basel , Switzerland ., Gondi G; d Department of Otorhinolaryngology , Klinikum der Universität München , Munich , Germany , and.; e Helmholtz Zentrum München - German Research Center for Environmental Health, Research Unit Gene Vectors , Munich , Germany., Zeidler R; d Department of Otorhinolaryngology , Klinikum der Universität München , Munich , Germany , and.; e Helmholtz Zentrum München - German Research Center for Environmental Health, Research Unit Gene Vectors , Munich , Germany., van Dijk M; b 4-Antibody AG (Wholly-Owned Subsidiary of Agenus Inc., USA) , Basel , Switzerland ., Zippelius A; a Department of Biomedicine , University of Basel , Basel , Switzerland .; c Department Internal Medicine , University Hospital Basel , Basel , Switzerland ., Renner C; a Department of Biomedicine , University of Basel , Basel , Switzerland .
Jazyk: angličtina
Zdroj: Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2015 Dec; Vol. 30 (6), pp. 955-60. Date of Electronic Publication: 2015 Sep 04.
DOI: 10.3109/14756366.2014.1001754
Abstrakt: Carbonic anhydrase 9 (CA9) and carbonic anhydrase 12 (CA12) were proposed as potential targets for cancer therapy more than 20 years ago. However, to date, there are only very few antibodies that have been described to specifically target CA9 and CA12 and also block the enzymatic activity of their targets. One of the early stage bottlenecks in identifying CA9- and CA12-inhibiting antibodies has been the lack of a high-throughput screening system that would allow for rapid assessment of inhibition of the targeted carbon dioxide hydratase activity of carbonic anhydrases. In this study, we show that measuring the esterase activity of carbonic anhydrase offers a robust and inexpensive screening method for identifying antibody candidates that block both hydratase and esterase activities of carbonic anhydrase's. To our knowledge, this is the first implementation of a facile surrogate-screening assay to identify potential therapeutic antibodies that block the clinically relevant hydratase activity of carbonic anhydrases.
Databáze: MEDLINE
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