Characterization of the binding of a novel antitumor drug ibrutinib with human serum albumin: Insights from spectroscopic, calorimetric and docking studies

Journal of Photochemistry and Photobiology. B, Biology
Bin TangHui Li

Abstract

Ibrutinib (IBR) is a novel Bruton's tyrosine kinase inhibitor and shows good efficacy for several B-cell malignancies. In the current study, the molecular mechanism of the interaction between IBR and the transport protein human serum albumin (HSA) was ascertained by spectroscopic, calorimetric, and docking studies. Detailed investigations on affinity parameter, binding model, conformational change, and site selectivity were implemented by receptor-based and ligand-based analysis. An unusual fluorescence co-quenching (mutual quenching) was observed in the binding of IBR to HSA, followed by a static mechanism. Fluorescence spectroscopy and isothermal titration calorimetry indicated that the binding affinity was at 104 M-1 level and electrostatic interactions and hydrophobic forces contributed the interaction. UV-vis and 3D fluorescence spectroscopy suggested the conformational changes of HSA after binding with IBR. Fourier transform infrared and circular dichroism spectroscopy further verified the variation in the secondary structure of HSA. Site-markers competition and molecular docking confirmed that IBR preferably binds to HSA at the cysteine-rich region of Sudlow's site I (subdomain IIA). This study systematically clarified t...Continue Reading

Citations

May 26, 2020·Journal of Biomolecular Structure & Dynamics·Mohd AmirSaleem Javed
Mar 29, 2020·Royal Society Open Science·Abdulrahman A AlmehiziaAli Saber Abdelhameed
Jul 18, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Xiaolan LvXun Tuo

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