Interaction of anti-cancer drug-cisplatin with major proteinase inhibitor-alpha-2-macroglobulin: Biophysical and thermodynamic analysis

International Journal of Biological Macromolecules
Mohammad Khalid ZiaFahim Halim Khan

Abstract

Alpha-2-macroglobulin is a multifunctional, highly abundant, plasma protein which reacts with a wide variety of molecules and drugs including cisplatin. Cisplatin is commonly used anticancer drug widely used for treatment of testicular, bladder, ovarian, head and neck, lung and cervical cancers. This study is designed to examine the interaction of cisplatin with human alpha-2-macroglobulin through various biophysical techniques and drug binding through molecular modeling. Cisplatin alters the function of alpha-2-macroglobulin and the thiolesters are most likely the reactive sites for cisplatin. Our result suggests that cisplatin decreases the antiproteolytic potential and causes structural and functional change in human alpha-2-macroglobulin as evident by absorption and fluorescence spectroscopy. Change in secondary structure of alpha-2-macroglobulin was confirmed by CD and FTIR. Thermodynamics parameters such as entropy (ΔS), enthalpy (ΔH) and Gibb's free energy changes (ΔG) along with number of binding sites (N) of alpha-2-macroglobulin-cisplatin binding in solutions were determined by isothermal titration calorimetry (ITC). It was found that binding of cisplatin with alpha-2-macroglobulin was exothermic in nature. The intera...Continue Reading

Citations

Sep 24, 2019·Journal of Biomolecular Structure & Dynamics·Tooba SiddiquiFahim Halim Khan
Jul 22, 2019·Journal of Fluorescence·Tooba SiddiquiFahim Halim Khan
Jun 15, 2021·International Journal of Biological Macromolecules·Georges JourdiPascale Gaussem

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