Lack of effect of the length of oligoglycine- and oligo(ethylene glycol)-derived para-substituents on the affinity of benzenesulfonamides for carbonic anhydrase II in solution

Article abstract of DOI:10.1021/ja00091a005

Using ₁H NMR spectroscopy, values of T₂ have been determined for the methylene protons of the oligoglycine moieties of para-substituted benzenesulfonamides having structures H₂NO₂SC₆H₄CO(Gly)(n)OH (n = 1-6) bound at the active site of bovine carbonic anhydrase II (CA, EC 4.2.1.1). These values have been correlated with measurements of dissociation constants of these complexes, in order to infer motion of these ligands when bound to the enzyme. Motion of glycines 1-3 (those closest to the aryl ring) is hindered by their proximity to the protein; motion of glycines 4-6 is relatively unhindered. Despite the restriction to motion inferred for glycines 1-3, the values of K(d) for the six compounds (n = 1-6, 1-6) are indistinguishable within experimental uncertainty (± 20%): K(d) in μM (n) 0.30 (1); 0.26 (2); 0.33 (3); 0.37 (4); 0.37 (5); 0.34 (6). There is, therefore, an unexpected compensation of the loss in conformational entropy on binding by another contributor to the free energy.