Esterase activity of carbonic anhydrases serves as surrogate for selecting antibodies blocking hydratase activity
| Autor: | Reinhard Zeidler, Alfred Zippelius, Marc Van Dijk, Gabor Gondi, Frank Stenner-Liewen, Christoph Renner, Petra Herzig, Volker Seibert, Philipp Müller, Narasimha Rao Uda |
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| Rok vydání: | 2015 |
| Předmět: |
High-throughput screening
Cancer therapy Esterase Structure-Activity Relationship Antigens Neoplasm Carbonic anhydrase Drug Discovery Screening method Humans Enzyme Inhibitors Carbonic Anhydrase IX Carbonic Anhydrases Aconitate Hydratase Pharmacology chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure biology Esterases Antibodies Monoclonal General Medicine Molecular biology Rapid assessment Acetazolamide Enzyme Biochemistry chemistry biology.protein Antibody |
| DOI: | 10.6084/m9.figshare.1568182.v2 |
| Popis: | 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: | OpenAIRE |
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