Effect of protein concentration on the binding of gold(I) to human serum albumin.

The binding of aurothiosulphate, gold(I), by human serum albumin has been studied by equilibrium dialysis at four different albumin concentrations, 37 degrees, pH 7.2-7.4 and ionic strength 0.15 M. The results show that the interaction of aurothiosulphate with albumin depends on albumin concentration. This observation is linked with the previous observation that the usual independent site description cannot be used to represent the clinically important low concentration data. All the observed dependences are satisfactorily accounted for by assuming that gold(I) competes with a highly bound contaminant for the high affinity (Cys(34)-SH) site. This description is supported by the experimental observation that a fraction of this site is originally blocked both in vivo and in in vitro. The present interpretation yields a high affinity binding constant 100 times larger than found previously and provides an explanation for the lack of correlation between dose and therapeutic and toxic effects in chrysotherapy.