Mitochondrial Targeting of Selective Electron Scavengers: Synthesis and Biological Analysis of Hemigramicidin-TEMPO Conjugates

摘要

The chemistry and biology of mitochondria, in particular, the effects of intracellular reactive oxygen species (ROS, superoxide radicals and H_2O_2) that are byproducts of the oxidative phospho-rylation cascade, is under intense study. Cellular injury, aging, and death, as well as suspended animation, neuro-, and cardioprotection are influenced by events in the mitochondrial membrane that lead to an imbalance in ATP production and O_2 consumption. Recently, dysregulated electron transport and generation of ROS were linked to a mitochondria-specific phospholipid, cardiolipin (CL), and involvement of CL oxidation products in apoptosis. Nitroxide radicals prevent the formation of ROS, particularly superoxide, due to their reduction by the mitochondrial electron transport to hydroxylamine radical scavengers. Nitroxides also exert superoxide dismutase and catalase activities, thus offering additional protective benefits against oxidative stress. However, delivery of sufficient amounts of nitroxides into mitochondria has proven difficult.