Hormonotoxins: abrogation of ribosome inactivating property of gelonin in the disulfide linked ovine luteinizing hormone-gelonin conjugates.
In order to synthesize a bioeffective hormonotoxin for selective targeting to specific cells in the gonads, gelonin, a single chain ribosome-inactivating protein obtained from an Indian plant called Gelonium multiflorum was covalently linked to ovine luteinizing hormone (oLH) by a disulfide bond. Ovine LH-S-S-gelonin conjugates of different molar ratios were subjected to determine the ribosome-inactivating property in a cell-free translation assay using rabbit reticulocyte lysate system. A single amino group modification with N-succinimidyl-3-(2-pyridyldithio)propionate resulted in a loss of 90% protein synthesis inhibition activity. Upon conjugation of gelonin to oLH, the activity was further inhibited ranging from 2.5-6.4%. A 1:1 to 1:1.5 molar ratio (oLH-S-S-gelonin) conjugates showed 2.5-4.6% activity while 1:2.8 to 1:2.2 molar ratio exhibited 5.5-6.4% inhibition ability.
Singh
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Institute of Self-Organizing Systems and Biophysics, North-Eastern Hill University, Meghalaya, India.
Curtiss
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R
D000818:Animals; D002474:Cell-Free System; D004220:Disulfides / Q000737:chemistry; D006728:Hormones / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use*; D007986:Luteinizing Hormone / Q000737:chemistry*; D010940:Plant Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000737:chemistry*; D011817:Rabbits; D054789:Ribosome Inactivating Proteins, Type 1; D012270:Ribosomes / Q000187:drug effects*; D012756:Sheep
D004220:Disulfides; D006728:Hormones; D000922:Immunotoxins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D007986:Luteinizing Hormone