Synthesis and Characterization of Polyaspartic Acid-Histidine Conjugate as an Analog of Antioxidant Enzymes

Abstract

Polyamino acids are versatile macromolecules with potential to be used as bioactive compounds and drug carriers. Polyaspartic acid (pAsp) and amide conjugate of pAsp with L-histidine (pAsp–His) were synthesized and their catalytic antioxidant properties were studied. pAsp–His did not exhibit the ability to decompose hydrogen peroxide. According to the redox reaction of generation of superoxide radical (SOR) by NADH/phenazine methosulfate, pAsp–His at a concentration of ≥0.1 mg/mL showed superoxide dismutase (SOD)-like activity similar to that of SOD-2 (100 U/mL). In addition, we showed that L-histidine in composition with manganese (II) and copper (II) ions catalyzed SOR dismutation in proportion to the amino acid concentration. SOD-like activity of pAsp–His was observed without addition of metal cofactors. The conjugate caused some cytotoxic effect towards cancer cells (PC-3 line, IC₅₀ ≈ 0.8 mg/mL, 72 h) and modulated viability human skin fibroblasts. The results are of particular interest for the development of bioactive peptides, which mimic action of natural enzymes.