[Studies on D-penicillamine (1): Inhibitory effect of D-penicillamine on the heat-Cu++ induced denaturation of human gamma-globulin (author's transl)].
The inhibitory effect of D-penicillamine on the denaturation of human gamma-globulin induced by heat and Cu++ was compared with the action of other agents such as antirheumatic drugs, anti-inflammatory drugs, SH reagents, SH inhibitors and chelating reagents. The denaturation of human gamma globulin was induced by Cu++ at 10 micrometer ("Cu++ induced denaturation") and was further increased by heating at 63 degrees C for 3 hr in the presence of Cu++ ("total denaturation"). Thus the value obtained by subtracting "Cu++ induced denaturation" from "total one" was designated as "thermal denaturation". D-Penicillamine enhanced "thermal denaturation" at a low concentration but inhibited it with increasing the concentration as well as L-cysteine. SH reagents such as thiomalic acid, 6-mercaptopurine inhibited "total" and "thermal" denaturation. SH inhibitors and protein binding reagents such as N-ethylmaleimide, trinitrobenzenesulfonic acid inhibited the "total" and "thermal" denaturation of the protein. Chelating reagents such as ethylenediamine tetraacetic acid, 8-hydroxyquinoline inhibited "total", "Cu++ induced" and "thermal" denaturation of the protein. Au+ inhibited "total denaturation", but not "Cu++ induced denaturation". On the other hand, Au+++ denaturated the protein considerably with or without heating, in the absence of Cu++ but dithiothreitol did so only with heating in the same condition. The anti-inflammatory drugs used herein had no effect on the protein denaturation. D-Penicillamine apparently prevents the denaturation of human gamma-globulin by the chelate formation with Cu++ and the binding to free protein SH, initiator for sulfhydryldisulfide interchange reaction.
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology; D006046:Gold / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D008301:Maleimides / Q000494:pharmacology; D015122:Mercaptopurine / Q000494:pharmacology; D010396:Penicillamine / Q000494:pharmacology*; D011485:Protein Binding; D011489:Protein Denaturation / Q000187:drug effects*; D012710:Serum Albumin, Bovine; D013870:Thiomalates / Q000494:pharmacology; D005719:gamma-Globulins
D001557:Benzenesulfonates; D002614:Chelating Agents; D008301:Maleimides; D013870:Thiomalates; D005719:gamma-Globulins; D012710:Serum Albumin, Bovine; D006046:Gold; D003300:Copper; D015122:Mercaptopurine; D010396:Penicillamine; D003545:Cysteine