Preparation And Characterization Of Cu, Zn-Superoxide Dismutase Covalently Modified By Polyunsaturated Fatty Acids

The generation of excessive reactive oxygen species in human, leading to significant damage of cellular biomolecules such as proteins, lipids and nucleic, is implicated in the initiation and progression of many human diseases. In this sense, inflammation, diabetes, cancer and neurodegenerative diseases are directly mediated by reactive oxygen species overproduction. Superoxide dismutases are essential metalloenzymes that eliminate superoxide radical, and thus protect cells from damage induced by free radicals, which have been proposed as an ideal Pharmaceuticals for preventing and treating these diseases. Unfortunately, the practical application of SOD was limited by its short plasma half life less than 6 min in vivo, insufficient stability, and cell membrane impermeability. In this study, Chemically modified Cu,Zn-superoxide dismutase (SOD) with linoleic acid andα-linolenic acid were achieved through two different synthetic methods to improve the stability and lipophilicify. Higher enzymatic activity retained has been observed compared with macromolecular substances modified SOD. The stabilities of the modified enzyme to heat, acid, alkali, and pepsin and trypsin treatment were investigated, and its apparent oil-water partition coefficient was also evaluated. Enhanced heat stability, acid and alkali resistance, anti-pepsin, and anti-trypsin stability of the modified SOD were observed compared with those of nature one, especially the apparent oil-water partition coefficient was increased. The results indicated that polyunsaturated fatty acids modified superoxide dismutases with enhanced stabilities and better bioavailability were promising for pharmacological properties investigation.