Reactions of carbon fourteen-benzyl-penicillin and carbon fourteen-benzyl-penicilloic acid with human red blood cell ghosts

Both [14C]-benzylpenicillin and [14C]-benzylpenicilloic acid reacated rapidly with human red blood cell ghosts (FRBCG)1 and human fibroblasts in isotonic phosphate buffer at 37? C. Of the total label bound to FRBCG exposed to either radioactive compound, approximately 40% could be removed by treating the labeled (FRBCG) with various thiols or neutral hydroxylamine. Treatment of (FRBCG) with thiols prior to their exposure to either radioactive compound decreased binding. Exposure of either [14C]-benzylpenicillin and [14C]-benzylpenicilloic acid to sulfhydryl-specific reagents also reduced binding substantially. The data are consistent with they hypothesis that rearrangement products of [14C]-benzylpenicillin and [14C]-benzylpenicilloic acid react with human proteins in a thiol-disulfide interchange type reaction. The rapid reaction of solutions of benzylpenicillin with model disulfides in a thiol-disulfide interchange reaction support this hypothesis.