Molecular Pharmacology, Vol 12, 279-290, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

A Nuclear Magnetic Resonance Study of the Kinetics of the Binding of the Renal Contrast Medium Acetrizoate to Albumin

¹ Departments of Pharmacology and Biophysical Chemistry, University of Nijmegen, Nijmegen, The Netherlands

NMR line broadening and shift measurements in conjunction with dialysis binding experiments have been performed on the acetrizoate-bovine serum albumin (BSA) system. Two types of binding sites have been detected, for which the binding constants and the kinetic parameters have been determined. The association rate constants for the formation of both types of acetrizoate-BSA complexes appear not to be diffusion-limited. The kinetic parameters are discussed in relation to the renal tubular excretion of acetrizoate. The acetrizoate molecules bound to the second class of binding sites retain a considerable amount of freedom with respect to the albumin molecule. It is pointed out that some earlier NMR studies concerning the motional freedom of individual molecular groups of pharmacologically interesting molecules on protein surfaces should be regarded with caution.

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ACKNOWLEDGMENTS The technical assistance of A. J. G. M. Henderix and J. W. M. van Kessel is gratefully acknowledged.