title: Spectroscopic and molecular modeling approaches to investigate the binding of proton pump inhibitors to human serum albumin.
abstract: The interaction between two proton pump inhibitors viz., omeprazole (OME) and esomeprazole (EPZ) with human serum albumin (HSA) was studied by fluorescence, absorption, circular dichroism (CD), Fourier transform infrared spectroscopy (FT-IR), voltammetry, and molecular modeling approaches. The Stern-Volmer quenching constants (Ksv) for OME-HSA and EPZ-HSA systems obtained at different temperatures revealed that both OME and EPZ quenched the intensity of HSA through dynamic mode of quenching mechanism. The binding constants of OME-HSA and EPZ-HSA increased with temperature, indicating the increased stability of these systems at higher temperatures. Thermodynamic parameters viz., ∆H°, ∆S°, and ∆G°were determined for both systems. These values revealed that both systems were stabilized by hydrophobic forces. The competitive displacement and molecular docking studies suggested that OME/EPZ was bound to Sudlow's site I in subdomain IIA in HSA. The extent of energy transfer from HSA to OME/EPZ and the distance of separation in tryptophan (Trp214) Trp214-OME and Trp214-EPZ was determined based on the theory of fluorescence resonance energy transfer. UV absorption, 3D fluorescence, and CD studies indicated that the binding of OME/EPZ to HSA has induced micro environmental changes around the protein which resulted changes in its secondary structure.
authors: a Department of Chemistry , Karnatak University , Dharwad 580003 , India.
authors: Suma K
authors: SK
authors: Pawar
authors: a Department of Chemistry , Karnatak University , Dharwad 580003 , India.
authors: Reeta
authors: R
authors: Punith
authors: a Department of Chemistry , Karnatak University , Dharwad 580003 , India.
authors: Roopa S
authors: RS
authors: Naik
authors: a Department of Chemistry , Karnatak University , Dharwad 580003 , India.
authors: J
authors: J
authors: Seetharamappa
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D054328:Proton Pump Inhibitors / Q000737:chemistry*; D000075462:Serum Albumin, Human / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
chemical_list: D054328:Proton Pump Inhibitors; D000075462:Serum Albumin, Human
keywords: HSA; circular dichroism; esomeprazole; fluorometry; molecular docking; omeprazole