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

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

Int J Biol Macromol. 2018 May 08;:

Authors: Zia MK, Siddiqui T, Ali SS, Ahsan H, Khan F

Abstract
Alpha-2-macroglobulin is a multifunctional, highly abundant, plasma protein which reacts with a wide variety of molecules and drugs such as 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) and affinity constant (K) of α2M-cisplatin binding in solutions were determined by isothermal titration calorimetry. It was found that binding of cisplatin with alpha-2-macroglobulin is exothermic in nature. The intake of the drug and presence of α2M in the blood plasma could likely facilitate their interaction which could lead to structural alterations in the conformational status of α2M.

PMID: 29751037 [PubMed - as supplied by publisher]

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