Development of a Functional Contrast Agent for Targeting Lipid-derived Radicals

Abstract

 Lipid derived radicals and their metabolic products are closely involved in the pathogenesis of oxidative stress diseases, such as inflammation and angiogenesis, through the formation of a protein or DNA complex. The starting point of lipid peroxide generation is lipid-derived radicals, which increase explosively via radical chain reaction. Therefore, the trapping of lipid-derived radicals is useful in understanding the mechanism of the formation of oxidative stress diseases, and in suppressing the following chain reaction. On the other hand, nitroxides with a stable unpaired electron allow for spin trapping with carbon-centered radicals. Hence, we focused on the following points to develop lipid radical detection methods. 1) Fluorescence will be quenched through interaction with nitroxide's unpaired electron. 2) Nitroxide can react with lipid-derived radicals via radical-radical reaction. 3) Fluorescence will recover from the loss of an unpaired electron in nitroxide, after reaction with the lipid-derived radicals, by using a profluorescent nitroxide. In this paper, I will discuss the development of a lipid-derived detection method using profluorescent nitroxide switching methods, and discuss its application to cell imaging.