Mitochondrial targeting of radioprotectants using peptidyl conjugates |
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Authors: | Kanai Anthony Zabbarova Irina Amoscato Andrew Epperly Michael Xiao Jingbo Wipf Peter |
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Affiliation: | Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. |
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Abstract: | Ionizing radiation activates a mitochondrial nitric oxide synthase, leading to inhibition of the respiratory chain, generation of excess superoxide, peroxynitrite production and nitrosative damage. We have measured the radioprotective effects of a nitric oxide synthase antagonist (AMT) versus a free radical scavenger (4-amino-TEMPO) using electrochemical detection of nitric oxide and peroxynitrite. To enhance their efficacy, we have conjugated these compounds to peptides and peptide isosteres--derived from the antibiotic gramicidin S--that target the mitochondria. The targeting ability of these peptidyl conjugates was measured using quantitative mass spectrometry. |
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