A new preparation of modified immune serum globulin (human) suitable for intravenous administration. I. Standardization of the reduction and alkylation reaction

Abstract

Immune serum globulin (ISG) prepared by Cohn cold alcohol fractionation of pooled human plasma was reduced with dithiothreitol (DTT) and alkylated with iodoacetamide and other alkylating agents. Our results show that there are a few labile interheavy chain disulfide bonds in ISG which react rapidly under mild, nondissociating conditions. The extent of disulfide cleavage is controlled primarily by the ratio of DTT to ISG until about 4-5 disulfide bonds have been reduced. We report detailed studies on the variables of ISG concentration, DTT to ISG ratio, pH, and time, leading to a chemically modified ISG that has a controlled and limited number of reduced and alkylated disulfide bonds.