AMINOSULFHYDRYL AND AMINODISULFIDE COMPOUNDS ENHANCE BINDING OF THE GLUCOCORTICOID RECEPTOR COMPLEX TO DEOXYRIBONUCLEIC ACID-COATED CELLULOSE AND TO CHROMATIN

In the presence of amine-containing sulfhydryl compounds, binding of h eat-transformed cytosolic mt liver glucocorticoid receptor complex (GR C) to double-stranded calf thymus DNA-coated cellulose and to rat live r chromatin was enhanced up to 10-fold. These observations were made u nder conditions when a maximum of 8% of the total GRC bound to DNA in the absence of test compound. Compounds which did not contain both a s ulfhydryl and amine group were inactive. Phosphorothioate derivatives of the active sulfhydryl compounds were also inactive. However, pretre atment of the phosphorothioate compounds with alkaline phosphatase res tored activity. Upon centrifugation at 8800g, amine-containing disulfi de compounds at millimolar concentrations caused considerable sediment ation of the GRC in the absence of DNA-coated cellulose or chromatin a nd no apparent increase in GRC binding to DNA or chromatin. Amine-cont aining disulfide compounds at micromolar concentrations did not cause heavy sedimentation of the GRC and enhanced binding of the GRC to DNA- coated cellulose up to 9.5-fold. Thus, diaminosulfhydryl compounds and the disulfide 1,18-diamino-6,13-diaza-9,10-dithiaoctadecane (WR 149,0 24) possess both the ability to restore and preserve the steroid bindi ng capacity of the glucocorticoid receptor and to enhance binding of t he GRC to DNA and chromatin.