Hormonotoxins: conjugation of human choriogonadotropin with the ribosome inactivating protein gelonin and comparison with a lutropin conjugate.
The properties of two hormonotoxins, human choriogonadotropin and ovine pituitary lutropin, each conjugated to the ribosome inactivating protein gelonin, have been compared. In both cases the linkage is effected through a disulfide bond provided by the cross-linker N-succinimidyl-3-(2-pyridyldithio)propionate. In each conjugate the hormone and toxin were calculated to be present in a ratio of 1:1. Immunological reactivity, receptor binding activity and steroidogenic activity of the hormonotoxins in radioimmunoassay or in membranes or cells containing LH receptors were reduced but not abolished in comparison with the thiolated hormones. Purified hormonotoxins were characterized by immunoassays specific for both interaction components, viz. the hormone (LH/hCG) and gelonin. Binding of the toxic component (gelonin) to the mouse Leydig tumour cells (MA-10 cells) was shown to occur via the hormone part of the hormonotoxins. This was effectively competed by the native hormone but not free gelonin. Both hormonotoxins were cytotoxic to MA-10 cells as protein synthesis was inhibited in their presence. This was associated with destruction of tumor cells in culture.
Singh
V
V
Reproduction Research Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
Sairam
M R
MR
D000818:Animals; D006063:Chorionic Gonadotropin / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D007986:Luteinizing Hormone / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D051379:Mice; D010940:Plant Proteins / Q000008:administration & dosage* / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D011967:Receptors, Gonadotropin / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D054789:Ribosome Inactivating Proteins, Type 1; D013736:Testicular Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D006063:Chorionic Gonadotropin; D010940:Plant Proteins; D011967:Receptors, Gonadotropin; D011974:Receptors, LH; D054789:Ribosome Inactivating Proteins, Type 1; D011374:Progesterone; C025674:GEL protein, Gelonium multiflorum; D007986:Luteinizing Hormone