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Monitoring subcellular biotransformation of N-l-leucyldoxorubicin by micellar electrokinetic capillary chromatography coupled to laser-induced fluorescence detection

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Abstract

Development of prodrugs is a promising alternative to address cytotoxicity and nonspecificity of common anticancer agents. N-l-leucyldoxorubicin (LeuDox) is a prodrug that is biotransformed to the anticancer drug doxorubicin (Dox) in the extracellular space; however, its biotransformation may also occur intracellularly in endocytic organelles. Such organelle-specific biotransformation is yet to be determined. In this study, magnetically enriched endocytic organelle fractions from human uterine sarcoma cells were treated with LeuDox. Micellar electrokinetic chromatography with laser-induced fluorescence detection (MEKC-LIF) was used to determine that 10 % of LeuDox was biotransformed to Dox, accounting for ∼43 % of the biotransformation occurring in the post-nuclear fraction. This finding suggests that endocytic organelles also participate in the intracellular biotransformation of LeuDox to Dox.

MEKC-LIF monitors the biotransformation of N-l-leucyldoxorubicin to doxorubicin specific to magnetically enriched endocytic organelles

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Acknowledgments

C.S. was supported by NIH grant T32 GM008347. B.M. was sponsored by the University of Minnesota’s Undergraduate Research Opportunities Program. We would like to thank Joseph J. Dalluge for his assistance with mass spectrometry and George Barany for his guidance on the synthesis of LeuDox.

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  1. Department of Chemistry, University of Minnesota Twin-Cities, 207 Pleasant St. SE, Minneapolis, MN, 55455-0431, USA

    Chad P. Satori, Brandon Meyer & Edgar A. Arriaga

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  1. Chad P. Satori
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  3. Edgar A. Arriaga
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Correspondence to Edgar A. Arriaga.

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Satori, C.P., Meyer, B. & Arriaga, E.A. Monitoring subcellular biotransformation of N-l-leucyldoxorubicin by micellar electrokinetic capillary chromatography coupled to laser-induced fluorescence detection. Anal Bioanal Chem 406, 2389–2397 (2014). https://doi.org/10.1007/s00216-014-7615-0

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