Development of Functional Models for a SOD

Ali Arslantas

doi:10.1155/mbd.2002.9

Abstract

Superoxide dismutase (SOD) is the scavenger of superoxide anion (O2−) and functions as a protector of living bodies. Study of a model compound of SOD is important when searching for the relationship between functions and structures of enzymes. Furthermore, SOD model compounds have potential for therapeutic usefulness. Although many SOD: model compounds have been reported, their structures are quite different from those of the native enzyme. Cu,Zn-SOD has been proposed for clinical uses. Unfortunately, many problems such as half-lifetime and antigenicity have not been overcome even though several copper(II) complexes are known to show SOD activity. Active oxygen species such as superoxide (O2−) from various components of the cellular electron transport chains, and provided during the respiratory burst of phagocytic cells, have been implicated both in the aging process and in degenerative diseases, including arthritis and cancer. Therefore, the biological system posseses the protective mechanisms against active species.

Highlights

The reactive superoxide radical anion, Oz, is a product of the oxygen metabolic cycle/1/
Some Fe/7, 9, 10/and Mn/7, 9, 11/Superoxide dismutase (SOD) mimics have been reported, and some of them show a marked SOD activity and seem to keep it in living cells/10, 11/. From all these results on native SODs or low molecular weight SOD mimics, it seems that the presence of coordination sites belonging to nitrogen heteroaromatic rings such as imidazoles or pyridines is important to have high SOD activity that is not affected by biological chelators/3, 10/
The following review briefly introduces the chemistry of the SOD enzymes, surveys recent advances in the synthesis of low molecular weight SOD mimics, and attempts to introduce some of the issues involved with the testing for SOD activity and the chemical design constraints one must satisfy in order to synthesize a highly active enzyme mimic which can function as a human pharmaceutical agent

Summary

INTRODUCTION

The reactive superoxide radical anion, Oz, is a product of the oxygen metabolic cycle/1/. The radical anion is a highly reactive toxic species in many biological systems. Oz dismutation very efficiently and it serves as an important means of defense against oxygen toxicity. It has been discovered /2/ that the superoxide dismutase enzymes catalyze disproportionation of the toxic superoxide ions into molecular oxygen and HzOz (Eq 1). Present address: K.T.B.K. 13 Nolu A Tipi Gida Kontro[ Mtif.

Development qfFunctional Modelsfor a SOD

MECHANISTIC ASPECTS

SUPEROXIDE DISMUTASE ACTIVITY

Ali Arslamas

CONCLUSION