| Abstract [eng] |
Carbonic anhydrases (CAs) are metalloenzymes that catalyze the conversion between carbon dioxide and bicarbonate. Their inhibition can be applied for treatment of different diseases, such as glaucoma, cancer, obesity, epilepsy, osteoporosis, etc. There are nearly 30 small molecule ligands that are used as drugs for carbonic anhydrase related diseases. In this work interaction between recombinant human carbonic anhydrases I, II, VII, IX, XIII and sulfonamide ligands was analysed. Stability of selected carbonic anhydrases was evaluated in different experimental conditions. Oligomeric structure of anticancer target CA IX was determined. Using carbonic anhydrases as model proteins, the application range of thermal shift assay was extended. Binding parameters of 40 new compounds to human carbonic anhydrases were measured. The binding thermodynamics of sulfonamide ligands to CA XIII was analyzed and intrinsic binding parameters, independent of the experimental conditions and linked protonation reactions, were determined. |
