Abstract
The interaction between bovine serum albumin and several anionic and cationic drugs was investigated using the electron spin resonance spin labeling technique. Albumin was covalently labeled with three different spin labels to monitor possible drug-induced conformational changes in its structure. The electron spin resonance spectra of the labeled bovine serum albumin in all cases consisted of two subspectra corresponding to a "partially immobilized" and a "strongly immobilized" label environment. The triazine (2,2,6,6-tetramethyl-4-dichlorotriazine aminopiperidine-1N-oxyl)—spin-labeled albumin proved most suitable for quantitation of the observed spectral changes. The anionic drugs tested caused an effect on the electron spin resonance spectra interpretable as a conversion of strongly immobilized sites to partially immobilized sites, probably as a result of unfolding of the bovine serum albumin molecule in the vicinity of the labeled histidine residue(s). The changes induced in the labeled bovine serum albumin spectra by acidic drugs were correlated with the degree of binding up to very high drug to protein ratios. These observations suggest that the spectral changes were due to a drug-induced conformational change in the bovine serum albumin with concomitant exposure of additional binding sites. In contrast to the anionic drugs, three tricyclic basic drugs, imipramine, desmethylimipramine, and fluphenazine, induced changes in the labeled bovine serum albumin spectrum exactly opposite to those observed with the acidic drugs—i.e., conversion of partially immobilized sites to strongly immobilized sites— while three nontricyclic basic drugs caused no detectable spectral changes. On the basis of available binding data, it is proposed that the effects of the basic drugs are also related to their degree of protein binding.
- Copyright ©, 1975, by Academic Press, Inc.
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