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. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.