Overview
Oxidative stress is known to play a role in various biological functions through reactive oxygen species (ROS), but the details are not clear. Therefore, our laboratory has developed caged peroxides, oxidative stress inducers are protected with photoprotective groups, for controlling the intracellular oxidative stress. Previously, we have developed BhcTBHP and MitoTBHP (Tsuji et al. Chem. Commun., 2023, 59, 6706). These caged compounds can rapidly release ter-butyl hydroperoxide (TBHP), an oxidative stress inducer, with irradiation. However, they required ultra-violet light (375 nm), concerned about cell damages, to release TBHP and are unstable to glutathione (GSH).
In this research, we designed and synthesized new caged peroxides, N6TBHP and N5TBHP to overcome these problems(Figure 1a). UV-vis spectra of N5TBHP and N6TBHP showed tailing toward longer wavelengths, which was not observed with BhcTBHP, when measured in 10 mM phosphate buffe (pH 7.4). We investigated photoreactivities of N5TBHP and N6TBHP at 455 nm because the absorption was observed above 455 nm. As a result, N6TBHP was most efficiently uncaged at 455 nm irradiation(Figure 1c).
Furthermore, when these caged compounds were treated with GSH (1 mM), we found that the stability of N6TBHP was significantly improved compared to BhcTBHP (Figure 2).
In cell imaging using the peroxide probe, we confirmed TBHP releasing from N6TBHP in cells by irradiation at 455 nm(Figure 3). Even though the concentration of N6TBHP was only 10 µM, the intensity indicated similar amount TBHP released from to the previous developed caged compound (50 µM).
The results of UV-vis spectra indicated their aggregation states were important for their photo reactivity and stability to GSH. By utilizing these properties, new caged peroxide with high intracellular stability and high photocleavable in visible light was successfully developed. The research results were published in "Bioorganic & Medicinal Chemistry" published by Elsevier.
Article information
Journal : Bioorganic & Medicinal Chemistry
The title of paper : Design and synthesis of visible light-activatable photocaged peroxides for optical control of ROS-mediated cellular signaling
Author : Mieko Tsuji *, Nobuyuki Koiso, Yufu Nishimura, Haruno Taira , Chinami Ogawa , Tasuku Hirayama , Hideko Nagasawa *
DOI number : 10.1016/j.bmc.2024.117863