Drug-protein interactions. Comparative studies of levamisole and structural analogs or agents with immunomodulatory effect on the mechanism of protein aggregation.

Interactions of tetramisole, imidazo[2,1-b]thiazolic derived or immunomodulatory agents with human serum albumin (HSA) and immunoglobulins G and A has been investigated in vitro using polyacrylamide gel electrophoresis and immunoelectrophoresis. The results suggest that only the chemical structure type of tetramisole is able to induce a protein-protein interaction described as a mechanism of disulfide-sulfhydryl interchange reactions. The groups of atoms involved in the interaction are characterized.

Drug-protein interactions. On the protein-protein interaction induced by levamisole in vitro. A mechanism hypothesis.

In the present communication, a model is reported in order to explain the aggregation of albumin induced by levamisole in vitro. The hypothesis suggests that the process of polymerization of albumins may include ligand-protein interaction as a biochemical catalysis, and covalent protein-protein interactions by a mechanism of disulfide-sulfhydryl interchange by intramolecular or intermolecular reactions.

Drug-protein interactions. A study of levamisole-serum albumin complex by 1H-NMR spectroscopy.

The chemical interaction of levamisole with human serum albumin (HSA) has been investigated using the technique of nuclear magnetic resonance spectroscopy. Binding to HSA occurs primarily with the imidazolidine and thiazolidine groups of levamisole as it has been demonstrated by selective changes in the relaxation times and the chemical shifts of the protons attached to the carbon atoms. The complex appears as the result of a weak linkage and may play a primordial role in the protein-protein interaction.

Drug-protein interactions. Inhibition of the action of levamisole on human serum albumin in vitro by DL-2-oxo-3-(2-mercaptoethyl)-5-phenyl-imidazolidine.

Comparative studies by polyacrylamide gel electrophoresis and immunoelectrophoresis showed that DL-2-oxo-3-(2-mercaptoethyl)-5-phenyl-imidazolidine (OMPI), a major metabolite of levamisole in vivo, exerted an inhibitory effect on the polymerization of albumin induced by levamisole action on human serum in vitro. Similar effects were obtained with sulfhydryl reagents. D-Penicillamine did not indicate such an action. The findings suggest that the SH groups of albumin may be involved in its interaction with levamisole.

Drug -- protein interactions in vitro. Effect of levamisole on human serum albumin.

The actions of (--)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]thiazole (levamisole) on human serum, human serum albumin (HSA) and bovin serum albumin (BSA) were studied. Analysis by polyacrylamide gel electrophoresis and immunodiffusion on gelose revealed the presence of aggregate forms of albumin in the human serum and a quantitative variation of polymeric forms with supplementary induced forms in case of HSA and BSA. The effect of other compounds with levamisole-like chemical groups including SH group or thiazolidine ring was investigated in similar conditions; aggregates were not observed. When the human serum was treated with these compounds, analysis by immunoelectrophoresis did not indicate a morphological change of lines of precipitate of immunoglobulins G and A previously described for levamisole action. The polymerization of albumin induced by the levamisole has been discussed. The whole of the data suggests that this drug may act in a specific way on the protein structure.

Drug protein interactions.

Effects of two antirheumatic drugs, D-penicillamine and (-)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b] thiazole (levamisole), on some human serum proteins with specific function are reported. Drug effects on the interaction corticosterone-corticosteroid binding globulin (CBG) in vitro were investigated especially by polyacrylamide gel electrophoresis. A quantitative modification of the % of corticosterone bound to CBG was noted. Drug effects on immunoglobulins involved in immune processes are described. Comparative studies by polyacrylamide gel electrophoresis and immunoelectrophoresis showed that addition of levamisole to the serum in vitro may give results different from those obtained when D-penicillamine was added. D-Penicillamine treatment was shown to induce principally a modification of Ig M, whereas levamisole caused a modification of Ig G and Ig A. On the other hand, "abnormal" fractions were noted by disc polyacrylamide gel electrophoresis when the serum was incubated with levamisole.