Use of spectroscopic, zeta potential and molecular dynamic techniques to study the interaction between human holo-transferrin and two antagonist drugs: Comparison of binary and ternary systems

Kabiri, M. and Amiri-Tehranizadeh, Z. and Baratian, A. and Saberi, M. R. and Chamani, J. (2012) Use of spectroscopic, zeta potential and molecular dynamic techniques to study the interaction between human holo-transferrin and two antagonist drugs: Comparison of binary and ternary systems. Molecules, 17 (3). pp. 3114-3147.

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Abstract

For the first time, the binding of ropinirole hydrochloride (ROP) and aspirin (ASA) to human holo-transferrin (hTf) has been investigated by spectroscopic approaches (fluorescence quenching, synchronous fluorescence, time-resolved fluorescence, three-dimensional fluorescence, UV-vis absorption, circular dichroism, resonance light scattering), as well as zeta potential and molecular modeling techniques, under simulated physiological conditions. Fluorescence analysis was used to estimate the effect of the ROP and ASA drugs on the fluorescence of hTf as well as to define the binding and quenching properties of binary and ternary complexes. The synchronized fluorescence and three-dimensional fluorescence spectra demonstrated some micro-environmental and conformational changes around the Trp and Tyr residues with a faint red shift. Thermodynamic analysis displayed the van der Waals forces and hydrogen bonds interactions are the major acting forces in stabilizing the complexes. Steady-state and time-resolved fluorescence data revealed that the fluorescence quenching of complexes are static mechanism. The effect of the drugs aggregating on the hTf resulted in an enhancement of the resonance light scattering (RLS) intensity. The average binding distance between were computed according to the forster non-radiation energy transfer theory. The circular dichroism (CD) spectral examinations indicated that the binding of the drugs induced a conformational change of hTf. Measurements of the zeta potential indicated that the combination of electrostatic and hydrophobic interactions between ROP, ASA and hTf formed micelle-like clusters. The molecular modeling confirmed the experimental results. This study is expected to provide important insight into the interaction of hTf with ROP and ASA to use in various toxicological and therapeutic processes.

Item Type: Article
Additional Information: Cited By :54 Export Date: 16 February 2020 CODEN: MOLEF Correspondence Address: Chamani, J.; Department of Biology, Faculty of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 9175687119, Iran; email: chamani@ibb.ut.ac.ir
Uncontrolled Keywords: Human holo-transferrin Molecular modeling Ropinirole hydrochloride Spectroscopic techniques Zeta potential acetylsalicylic acid indole derivative ropinirole transferrin algorithm article binding site chemical phenomena chemistry circular dichroism drug antagonism fluorescence resonance energy transfer human hydrogen bond light molecular dynamics protein binding protein secondary structure radiation scattering spectrofluorometry thermodynamics Algorithms Aspirin Binding Sites Humans Hydrogen Bonding Hydrophobic and Hydrophilic Interactions Indoles Molecular Dynamics Simulation Protein Structure, Secondary Scattering, Radiation Spectrometry, Fluorescence
Subjects: QU Biochemistry
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib5 lib5
Date Deposited: 13 May 2020 06:00
Last Modified: 13 May 2020 06:00
URI: http://eprints.mums.ac.ir/id/eprint/18908

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