In-vitro selective killing of gonadal cells by a hormonotoxin composed of ovine luteinizing hormone linked by a disulfide bond to the ribosome-inactivating protein, gelonin.
With the aim to synthesize a bioeffective hormonotoxin for selective targeting to specific cells in the gonads, a single chain RIP was conjugated to oLH with the use of SPDP which generated oLH-S-S-gelonin hormonotoxin. Extensive physico-chemical, immunochemical and biochemical characterization reveal that 1:1 oLH-gelonin was linked through the alpha-subunit of the oLH. The hormonotoxin retained substantial receptor binding and steroidogenic activity in the leydig tumor cells. The competitive displacement analysis indicate that the binding occurs via the hormone. The presently described hormonotoxin exhibited higher receptor binding and cytotoxicity to the target cells than that of others reported so far.
Singh
V
V
Institute of Self-Organising Systems and Biophysics, North-Eastern Hill University, Meghalaya, India.
Das
C
C
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D002850:Chromatography, Gel; D003198:Computer Simulation; D004220:Disulfides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006066:Gonads / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects; D007986:Luteinizing Hormone / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D010940:Plant Proteins / Q000737:chemistry / Q000633:toxicity*; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D011967:Receptors, Gonadotropin / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D014407:Tumor Cells, Cultured
D004220:Disulfides; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D011967:Receptors, Gonadotropin; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D007986:Luteinizing Hormone