Modulated Protein Binding Ability of Anti-Diabetic Drugs in Presence of Monodispersed Gold Nanoparticles and its Inhibitory Potential towards Advanced Glycated End (AGE) Product Formation.

Abstract

Binding strength of the anti-diabetic drugs chlorpropamide (CPM) and tolbutamide (TBM) with model protein bovine serum albumin (BSA) shows strong modulation in presence of colloidal gold nanoparticles (AuNP). Intrinsic tryptophan fluorescence of both the native BSA and BSA-AuNP conjugate quenched in presence of the drugs. Stern-Volmer quenching constant (KSV) of CPM binding to BSA-AuNP conjugate at different temperatures is almost twice (6.76~14.76 × 103M-1) than the corresponding values in native BSA (3.21~5.72 × 103M-1). However, the calculated KSV values with TBM show certain degree of reduction in presence of AuNP (6.46× 103M-1), while comparing with native BSA (8.83 × 103M-1). The binding mode of CPM towards BSA-AuNP conjugate is mainly through hydrophobic forces; whereas, TBM binding is identified to be Van der Waal's and hydrogen bonding type of interaction. Fluorescence lifetime analysis confirms static type of quenching for the intrinsic tryptophan fluorescence of BSA as well as BSA-AuNP conjugate with addition of CPM and TBM at different concentrations. The α-helical content in the secondary structure of BSA is decreased to 48.32% and 45. 28% in presence of AuNP, when the concentration of CPM is 0.08mM and 0.16mM in comparison with that of native protein (50.13%). On the other hand, the intensity of sugar induced advanced glycated end (AGE) product fluorescence is decreased by 55% and 80% at 0.13nM and 0.68nM AuNP, respectively. Change in the binding strength of the drugs with transport protein and reduced AGE product formation in presence of AuNP could lead to a major development in the field of nanomedicine and associated drug delivery techniques. Graphical Abstract Modulated drug binding ability and AGE product formation of serum proteins in presence of AuNP.