Thermodynamic Optimisation in Drug Discovery: A Case Study using Carbonic Anhydrase Inhibitors

Abstract

A systematic thermodynamic analysis of benzene sulfonamide derivatives binding to carbonic anhydrase revealed a unique change in enthalpy for one of the compounds investigated. Subsequent X-ray analysis showed a different binding mode for this compound and further optimization led to a high-affinity, enthalpy-driven compound, emphasizing the importance of thermodynamic profiling.