Kinetic aspects of structure — activity relationships in the carbonic anhydrase — sulphonamide system
The binding of sulphonamide inhibitors to the enzyme carbonic anhydrase (E.C.18.104.22.168) is a useful model system for the interaction of drugs with receptors. There exists a very wide range of chemically related specific inhibitors, all of those with high affinity (Ka>105 M−1) possessing the following properties. The sulphonamide group is unsubstituted on the nitrogen atom and is directly linked to an aromatic nucleus. This nucleus may be homocyclic, of the benzene or naphthalene type, or it maybe heterocyclic, as in the case of the well-known drugs acetazolamide and chlorothiazide. The enzyme itself is easily purified in large quantities from mammalian blood and has the useful qualities of being extremely stable to a wide variety of storage and experimental conditions. The physical properties of the enzyme have been closely studied and an X-ray structure is available. Most of the following studies have been carried out using the C isoenzyme of human carbonic anhydrase(HCA-C).
KeywordsCarbonic Anhydrase Binding Constant Affinity Constant Dissociation Rate Constant Kinetic Aspect
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