Improved pharmacological properties for superoxide dismutase modified with mannan

Area of Science:

• Biochemistry
• Biomaterials Science
• Enzyme Engineering

Background:

• Superoxide dismutase (SOD) is a crucial antioxidant enzyme.
• SOD's therapeutic application is limited by its short plasma half-life and susceptibility to oxidative damage.
• Mannan, a polysaccharide from Saccharomyces cerevisiae, can be chemically modified.

Purpose of the Study:

• To chemically modify SOD by glycosylation with mannan to enhance its stability and therapeutic properties.
• To investigate the impact of mannan conjugation on SOD's activity, stability, and pharmacokinetic profile.

Main Methods:

• Mannan from Saccharomyces cerevisiae was oxidized using sodium m-periodate (NaIO(4)).
• Oxidized mannan was conjugated to SOD via reductive alkylation using sodium borohydride (NaBH(4)).
• The resulting glycosylated SOD was characterized for its polysaccharide content, enzyme activity, stability, and lectin-binding properties.

Main Results:

• The glycosylated SOD contained an average of 1.2 mol of mannan per mol of protein, retaining 52% of its initial activity.
• The modified SOD exhibited 560-fold increased resistance to hydrogen peroxide (H(2)O(2)) inactivation.
• Conjugation with mannan enhanced SOD's anti-inflammatory activity twofold and prolonged its plasma half-life from 4.8 minutes to 1.7 hours.

Conclusions:

• Mannan conjugation significantly enhances the stability and therapeutic potential of superoxide dismutase.
• Glycosylated SOD demonstrates improved resistance to oxidative stress and extended in vivo circulation time.
• This modified SOD holds promise for treating inflammatory conditions and oxidative stress-related diseases.