LACK OF EFFECT OF THE LENGTH OF OLIGOGLYCINE-DERIVED AND OLIGO(ETHYLENE-GLYCOL)-DERIVED PARA-SUBSTITUENTS ON THE AFFINITY OF BENZENESULFONAMIDES FOR CARBONIC-ANHYDRASE-II IN SOLUTION
A. Jain et al., LACK OF EFFECT OF THE LENGTH OF OLIGOGLYCINE-DERIVED AND OLIGO(ETHYLENE-GLYCOL)-DERIVED PARA-SUBSTITUENTS ON THE AFFINITY OF BENZENESULFONAMIDES FOR CARBONIC-ANHYDRASE-II IN SOLUTION, Journal of the American Chemical Society, 116(12), 1994, pp. 5057-5062
Using H-1 NMR spectroscopy, values of T-2 have been determined for the
methylene protons of the oligoglycine moieties of para-substituted be
nzenesulfonamides having structures H2NO2SC6H4CO(Gly)(n)OH (n = 1-6) b
ound at the active site of bovine carbonic anhydrase II (CA, EC 4.2.1.
1). These values have been correlated with measurements of dissociatio
n constants of these complexes, in order to infer motion of these liga
nds 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 m
otion inferred for glycines 1-3, the values of K-d for the six compoun
ds (n = 1-6, 1-6) are indistinguishable within experimental uncertaint
y (+/-20%): K-d in mu M (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 t
he loss in conformational entropy on binding by another contributor to
the free energy.