2-Methoxy-4-formylphenol suppresses methylglyoxal glycation mediated structural alterations and esterase activity of...

Glycation is the non-enzymatic reaction of glucose or its metabolites to proteins, causing irreversible changes. Methylglyoxal, a dicarbonyl, affects the structure and function of physiologically important proteins. Being a major circulatory protein, hemoglobin is highly prone to glycation. Current research focuses on identifying potent glycation inhibitors to prevent glycation and their impact on protein structure and function. The present study investigates the Advanced Glycation Endproducts (AGEs) inhibitory effects of 2-methoxy-4-formylphenol (Vanillin) against methylglyoxal mediated glycation of hemoglobin. The hemoglobin-vanillin glycation model exhibited inhibition of AGE formation, amyloid fibrils, aggregates and reduction in esterase activity. The fluorescence spectroscopic technique revealed efficient binding of vanillin and hemoglobin, with Stern Volmer plot indicating the presence of static quenching. The conformational stability of the vanillin and hemoglobin interaction was also evident from the molecular docking and dynamics studies. The proximal orientation of residues (H2 and K82 associated in esterase activity) of hemoglobin β1 chain and vanillin, supports the noted effect of reduced esterase activity in the presence of vanillin in glycated hemoglobin and the inhibition of the overall formation of AGE of hemoglobin in the presence of vanillin.