Affinity and Selectivity of Protein-Ligand Recognition: A Minor Chemical Modification Changes Carbonic Anhydrase Binding Profile.

ABSTRACT: Discovery of small-molecule drugs relies on their strong binding affinity compared to nontarget proteins, thus possessing selectivity. Minor chemical structure changes usually exhibit little change in the compound efficacy, with rare exceptions. We developed a series of nearly 50 ortho-substituted benzenesulfonamides and experimentally measured their interactions with the 12 catalytically active human carbonic anhydrase (CA) isozymes. Inhibitors were designed using seven different substituent groups, including 4-sulfanyl-substituted 3-sulfamoyl benzoates and benzamides, 4-sulfinyl-substituted 3-sulfamoyl benzoates and benzamides, 4-sulfonyl-substituted 3-sulfamoyl benzoates and benzamides, and 4-amino-substituted benzamides. The oxidation state of sulfur at the

SUBMITTER: Zaksauskas A 

PROVIDER: S-EPMC12406193 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature