Mitochondrial targeting of radioprotectants using peptidyl conjugates.
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.
Kanai
Anthony
A
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Zabbarova
Irina
I
Amoscato
Andrew
A
Epperly
Michael
M
Xiao
Jingbo
J
Wipf
Peter
P
D000818:Animals; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004563:Electrochemistry; D006096:Gramicidin / Q000737:chemistry; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D009569:Nitric Oxide / Q000737:chemistry*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010455:Peptides / Q000737:chemistry*; D030421:Peroxynitrous Acid / Q000737:chemistry*; D013367:Submitochondrial Particles / Q000737:chemistry; D013481:Superoxides
D003497:Cyclic N-Oxides; D010455:Peptides; D013481:Superoxides; D006096:Gramicidin; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C003959:TEMPO