Solid Phase Synthesis of Mitochondrial Triphenylphosphonium-Vitamin E Metabolite Using a Lysine Linker for Reversal of Oxidative Stress

Mohanad Mossalam; Jamie Soto; Carol S Lim; E. Dale Abel

doi:10.1371/journal.pone.0053272

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Solid Phase Synthesis of Mitochondrial Triphenylphosphonium-Vitamin E Metabolite Using a Lysine Linker for Reversal of Oxidative Stress

Journal article

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Solid Phase Synthesis of Mitochondrial Triphenylphosphonium-Vitamin E Metabolite Using a Lysine Linker for Reversal of Oxidative Stress

Mohanad Mossalam, Jamie Soto, Carol S Lim and E. Dale Abel

PloS one, Vol.8(1), pp.e53272-e53272

01/18/2013

DOI: 10.1371/journal.pone.0053272

PMCID: PMC3544826

PMID: 23341934

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Abstract

Mitochondrial targeting of antioxidants has been an area of interest due to the mitochondria's role in producing and metabolizing reactive oxygen species. Antioxidants, especially vitamin E (α-tocopherol), have been conjugated to lipophilic cations to increase their mitochondrial targeting. Synthetic vitamin E analogues have also been produced as an alternative to α-tocopherol. In this paper, we investigated the mitochondrial targeting of a vitamin E metabolite, 2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman (α-CEHC), which is similar in structure to vitamin E analogues. We report a fast and efficient method to conjugate the water-soluble metabolite, α-CEHC, to triphenylphosphonium cation via a lysine linker using solid phase synthesis. The efficacy of the final product (MitoCEHC) to lower oxidative stress was tested in bovine aortic endothelial cells. In addition the ability of MitoCEHC to target the mitochondria was examined in type 2 diabetes db/db mice. The results showed mitochondrial accumulation in vivo and oxidative stress decrease in vitro.

Medicine

Chemistry

Biology

Details

Title: Subtitle: Solid Phase Synthesis of Mitochondrial Triphenylphosphonium-Vitamin E Metabolite Using a Lysine Linker for Reversal of Oxidative Stress
Creators: Mohanad Mossalam
Jamie Soto
Carol S Lim
E. Dale Abel
Resource Type: Journal article
Publication Details: PloS one, Vol.8(1), pp.e53272-e53272
DOI: 10.1371/journal.pone.0053272
PMID: 23341934
PMCID: PMC3544826
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; San Francisco, USA
Alternative title: Synthesis of Mitochondrially Targeted Alpha-CEHC
Language: English
Date published: 01/18/2013
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024529602771

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