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- W2016977317 abstract "V-PYRRO/NO is a well studied nitric oxide (NO) prodrug which has been shown to protect human liver cells from arsenic, acetaminophen, and other toxic assaults in vivo. Its proline-based analogue, V-PROLI/NO, was designed to be a more biocompatible form that decomposes to the naturally occurring metabolites of proline, NO, and glycolaldehyde. Like V-PYRRO/NO, this cytochrome P450-activated prodrug was previously assumed to passively diffuse through the cellular membrane. Using (14)C-labeled proline in a competition assay, we show that V-PROLI/NO is transported through proline transporters into multiple cell lines. A fluorescent NO-sensitive dye (DAF-FM diacetate) and nitrite excretion indicated elevated intracellular NO release after metabolism over V-PYRRO/NO. These results also allowed us to predict and design a more permeable analogue, V-SARCO/NO. We report a proline transporter-based strategy for the selective transport of NO prodrugs that may have enhanced efficacy and aid in development of further NO prodrugs with increased permeability." @default.
- W2016977317 created "2016-06-24" @default.
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- W2016977317 date "2010-07-28" @default.
- W2016977317 modified "2023-09-25" @default.
- W2016977317 title "The Nitric Oxide Prodrug V-PROLI/NO Inhibits Cellular Uptake of Proline" @default.
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- W2016977317 doi "https://doi.org/10.1021/ml1000905" @default.
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