Spectroscopic and molecular modelling studies on glycation modified bovine serum albumin with cyanidin-3-O-glucoside

In this study, we report the glycation mediated effect of bovine serum albumin (BSA) on the molecular interaction mechanism of cyanidin-3-O-glucoside (C3G) by molecular modelling, Uv-visible spectroscopy, transmission electron microscopy (TEM), fluorescence spectroscopy, and circular dichroism spectroscopy studies. The structures of advanced glycation end-products (AGEs) modified BSA were modelled, energy minimized and analyzed for binding affinity by molecular docking studies using Autodock Vina. Glycation experiments are carried out using glucose and methylglyoxal to validate the molecular modelling results on the interaction of modified BSA with C3G. The modified structures were characterized by reduction in the binding pocket volume, surface, depth, hydrophobicity, and hydrogen bond donors/acceptors. Arg-194, Arg-196, Arg-198, Arg-217, Arg-409, Lys-114, Lys-116, Lys-204, Lys 221, and Lys-439 were found to be crucial in the context of glycation of BSA. TEM images represented the formation of unique globular aggregates in the event of glycation. Uv-visible spectroscopic studies showed the formation of new chromophores between 300 and 400 nm in the event of glycation. Fluorescence quenching was observed in a differential manner in the presence of C3G on glycation modified BSA. Circular dichroism studies suggested the loss of helical structure and formation of β-sheeted structure upon glycation, but subsequent C3G binding has resulted in the increase towards helical structure. Our findings suggested that drug binding affinity has been certainly impaired due to glycation and subsequent AGE modification. Arg-p modification has more austere impact on the structure and would affect the binding properties. We conclude that C3G had differential modulation of binding properties on glycated BSA which can help to protect the stability and bioavailability that has been impaired due to glycation mediated structural changes.