Novel enzyme mimic could be used to help treat inflammatory diseases.

Breathing can be a dangerous business. If the body doesn't produce enough enzymes to mop up superoxide, a natural product of breathing, inflammatory disorders can develop. Now researchers from the University of York and King's College London claim to have synthesized a novel compound which mimics a key enzyme, manganese superoxide dismutase (SOD). This compound has easily tunable properties and comparable activity to compounds currently in clinical trials.

Superoxide (O₂^.-), an aggressive and destructive radical, is an unfortunate by-product of the breathing process, although it is only produced in small amounts. Nature has evolved superoxide dismutases to help remove superoxide before it can damage cells, but any that is not mopped up quickly enough can have devastating effects. Catalysts which remove superoxide quickly could be given to patients suffering from inflammatory disorders. SOD is a natural choice for a starting point. The enzyme works through a redox-couple between manganese(iii) and manganese(ii) and acid-base equilibria. By careful choice of ligand, Paul Walton and colleagues have shown that they can modify both components.

Looking to the future, Walton says: 'we aim to explore the relationships between redox potential, acid-base equilibria, ligand substituent and SOD activity in order to provide a mechanism for the rational design of more effective mimics'.

David Garner, a bioinorganic chemist from the University of Nottingham, considers that 'the system reported by Walton et al, or its chemical relatives, may have pharmaceutical applications for the treatment of inflammatory conditions in humans and animals, by removal of superoxide anions'.

Steven Evans