A mitochondria-targeted macrocyclic Mn(II) superoxide dismutase mimetic.

Abstract

Superoxide (O(2)(·-)) is the proximal mitochondrial reactive oxygen species underlying pathology and redox signaling. This central role prioritizes development of a mitochondria-targeted reagent selective for controlling O(2)(·-). We have conjugated a mitochondria-targeting triphenylphosphonium (TPP) cation to a O(2)(·-)-selective pentaaza macrocyclic Mn(II) superoxide dismutase (SOD) mimetic to make MitoSOD, a mitochondria-targeted SOD mimetic. MitoSOD showed rapid and extensive membrane potential-dependent uptake into mitochondria without loss of Mn and retained SOD activity. Pulse radiolysis measurements confirmed that MitoSOD was a very effective catalytic SOD mimetic. MitoSOD also catalyzes the ascorbate-dependent reduction of O(2)(·-). The combination of mitochondrial uptake and O(2)(·-) scavenging by MitoSOD decreased inactivation of the matrix enzyme aconitase caused by O(2)(·-). MitoSOD is an effective mitochondria-targeted macrocyclic SOD mimetic that selectively protects mitochondria from O(2)(·-) damage.

DOI: 10.1016/j.chembiol.2012.08.005

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@article{Kelso2012AMM, title={A mitochondria-targeted macrocyclic Mn(II) superoxide dismutase mimetic.}, author={Geoffrey F Kelso and Andrej Maroz and Helena M. Cochem{\'e} and Angela Logan and Tracy A. Prime and Alexander V. Peskin and Christine C. Winterbourn and Andrew M. James and Meredith F Ross and Sally Brooker and Carolyn M. Porteous and Robert F. Anderson and Michael P. Murphy and Robin A. J. Smith}, journal={Chemistry & biology}, year={2012}, volume={19 10}, pages={1237-46} }