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• W1909222731 endingPage "419" @default.
• W1909222731 startingPage "409" @default.
• W1909222731 abstract "Protein toxins, such as gelonin, are highly desirable anti-cancer drug candidates due to their unparalleled potency and repetitive reaction mechanism in inhibiting protein translation. However, for its potential application in cancer therapy, there remains the cell membrane barrier that allows permeation of only small molecules, which must be overcome. To address this challenge, we conjugated gelonin with a protein transduction domain (PTD), the TAT peptide, via genetic recombination. The chimeric TAT-gelonin fusion protein (TAT-Gel) retained equipotent N-glycosidase activity yet displayed greater cell uptake than unmodified recombinant gelonin (rGel), thereby yielding a significantly augmented cytotoxic activity. Remarkably, TAT-Gel displayed up to 177-fold lower IC₅₀ (avg. 54.3 nM) than rGel (avg. IC₅₀ : 3640 nM) in tested cell lines. This enhanced cytotoxicity, however, also raised potential toxicity concerns due to the non-selectivity of PTD in its mediated cell transduction. To solve this problem, we investigated the plausibility of regulating the cell transduction of TAT-Gel via a reversible masking using heparin and protamine. Here, we demonstrated, both in vitro and in vivo, that the cell transduction of TAT-Gel can be completely curbed with heparin and yet this heparin block can be efficiently reversed by the addition of protamine. This reversible tight regulation of the cell transduction of TAT-Gel by heparin and protamine sheds light of possible application of TAT-Gel in achieving a highly effective yet safe drug therapy for the treatment of tumors." @default.
• W1909222731 created "2016-06-24" @default.
• W1909222731 creator A5008737588 @default.
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• W1909222731 date "2014-04-23" @default.
• W1909222731 modified "2023-09-26" @default.
• W1909222731 title "Recombinant TAT-gelonin fusion toxin: Synthesis and characterization of heparin/protamine-regulated cell transduction" @default.
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• W1909222731 doi "https://doi.org/10.1002/jbm.a.35188" @default.
• W1909222731 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4198515" @default.
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• W1909222731 hasPublicationYear "2014" @default.
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