Binding site identification of metformin to human serum albumin and glycated human serum albumin by spectroscopic and molecular modeling techniques: a comparison study

The interaction between metformin and human serum albumin (HSA), as well as its glycated form (gHSA) was investigated by multiple spectroscopic techniques, zeta potential, and molecular modeling under physiological conditions. The steady state and time-resolved fluorescence data displayed the quench...

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Bibliographic Details
Published in:Journal of biomolecular structure & dynamics 2015-03, Vol.33 (3), p.513-533
Main Authors: Rahnama, Elaheh, Mahmoodian-Moghaddam, Maryam, Khorsand-Ahmadi, Sabra, Saberi, Mohammad Reza, Chamani, Jamshidkhan
Format: Article
Language:English
Subjects:
Binding Sites
Circular Dichroism
Energy Transfer
Fluorescence Polarization
gHSA
HSA
Humans
Hydrophobic and Hydrophilic Interactions
Hypoglycemic Agents - chemistry
metformin
Metformin - chemistry
Molecular Docking Simulation
molecular modeling
Protein Binding
Protein Structure, Secondary
Serum Albumin - chemistry
spectroscopy
Thermodynamics
zeta potential
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Summary:The interaction between metformin and human serum albumin (HSA), as well as its glycated form (gHSA) was investigated by multiple spectroscopic techniques, zeta potential, and molecular modeling under physiological conditions. The steady state and time-resolved fluorescence data displayed the quenching mechanism of HSA-metformin and gHSA-metformin was static. The binding information, including the binding constants, number of binding sites, effective quenching constant showed that the binding affinity of metformin to HSA was greater than to gHSA which also confirmed by anisotropy measurements. It was determined that metformin had two and one set of binding sites on HSA and gHSA, respectively. Far-UV CD spectra of proteins demonstrated that the α-helical content decreased with increasing metformin concentration. The zeta potential and resonance light scattering (RLS) diagrams provided that lower drug concentration induced metformin aggregation on gHSA surface as compare to HSA. The increase in polarizability was one of the important factors for the enhancement of RLS and the formation of drug/protein complexes. The zeta potential results suggested that both hydrophobic and electrostatic interactions played important roles in the protein-metformin complex formation. Site marker experiments and molecular modeling showed that the metformin bound to subdomain IIIA (Sudlow's site II) on HSA and gHSA.
ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2014.893540