Effects of therapeutically useful thiols (DL-penicillamine and alpha-mercaptopropionylglycine) on immunoglobulins.

The action of 0·05 M DL-penicillamine (DL-P) and α-mercaptopropionylglycine upon immunoglobulins, both in their native serum and after isolation, has been studied. IgM was always affected, apparently with breakdown of 19S polymers and release of 7S sub-units. This depolymerization leads both to a change in electrophoretic mobility and to increased diffusibility in gels, as well as to decrease in serum viscosity. IgG, as a rule, is not affected when studied in whole serum. The exception to the rule is provided by monoclonal proteins of the IgG3 subgroup. The observed effects are variable, and may consist of an increase in the electropositivity of the molecules, the release of light chains, or the splitting into Fab- and Fc-like fragments. IgA was irregularly affected. The results suggest that several types of action may be present: depolymerization of high molecular weight polymers, which seem to be more resistant to the action of DL-P than its IgM counterparts, unfolding of 7S molecules with increased electropositivity, and breakdown of 7S molecules into halves, each containing both H and L chains. Precipitation of cryoglobulins was inhibited by both thiols, both when added to whole serum or isolated proteins.