Interactions of disulfiram and diethyldithiocarbamate with serum proteins studied by means of a gel-filtration technique

Abstract

Tetraethylthiuram disulphide (disulfiram) and the corresponding thiol diethyldithiocarbamate in concentrations from 10 −6 to 10 −4 M have been quantitatively separated by means of gel filtration on a Sephadex G-25 column, using 35S-Iabelled compounds. Both the thiol and the disulphide possess distribution coefficients (K d) above unity, showing that they are adsorbed to the gel material. The K d of the disulphide (2.65) was considerably higher than that of the thiol (1.26). Quantitative recovery of the strong metal-complexing diethyldithiocarbamate was obtained only when the buffer used were freed of complexing metal ions by pretreatment with diphenylthiocarbazone. The interactions of diethyldithiocarbamate and disulfiram with serum proteins were studied by the gel filtration technique. The thiol was shown only to become loosely and reversibly adsorbed to the proteins. The disulphide reacted with the albumin fraction of the serum proteins by mixed disulphide formation with their—SH groups in an amount which corresponded to the known amount of titrable -SH groups of albumin.