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Gelonin is a 30 kDa type I ribosome-inactivating protein (RIP) derived from the seeds of Gelonium multiflorum, a Himalayan plant. It is a single-chain glycoprotein that acts as a potent N-glycosidase, selectively cleaving the adenine-4324 from 28S rRNA in the eukaryotic ribosome, thus irreversibly inactivating the ribosome and inhibiting protein synthesis, leading to cell death. Gelonin lacks a carbohydrate-binding (cell binding) domain, and thus cannot by itself cross cell membranes, making it highly potent in cell-free systems but with poor cytotoxicity when applied to intact cells. Its main research application has been as a cytotoxic payload for targeted anticancer therapeutics, including immunotoxins and fusion proteins with cell-penetrating or tumor-targeting moieties to enable cellular entry. Gelonin exerts pronounced antiproliferative and apoptotic effects when efficiently delivered intracellularly and has been explored in preclinical studies for cancer therapy. Its activity is comparable to other type I RIPs but with reported lower systemic toxicity, like reduced hepatotoxicity and lack of capillary leak syndrome, than some related plant toxins[1][2][3][5][7][8].
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