Exploring binding interaction of baricitinib with bovine serum albumin (BSA): multi-spectroscopic approaches combined with theoretical calculation

Abstract

Baricitinib (BRT) is an orally administered small molecule JAK inhibitor, which mainly inhibits JAK-1 and JAK-2. And it is used to treat autoimmune diseases such as rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus. In this paper, the interaction between BRT and bovine serum albumin (BSA) was studied by fluorescence spectroscopy, UV spectrophotometry, fourier transform infrared spectroscopy (FT-IR) and molecular docking approaches. It has been proved that the fluorescence quenching mechanism of BSA in the mutual complexation process of BRT and BSA was a static quenching. The number of binding sites (n) of BRT-BSA complex was about 1. The binding site was located at site II of BSA and its binding constant was about 5.01 × 103 M−1 at 298 k. It is indicated that there was a weak binding between BRT and BSA. By analyzing the sign and magnitude of the free energy change (ΔG0), enthalpy change (ΔH0) and entropy change (ΔS0), it can be found that the complexation process of BRT and BSA is spontaneous and enthalpy-driven. Van der Waals forces and hydrogen bonds play a critical part in the complexation process of BRT with BSA. Based on synchronous fluorescence and three-dimensional fluorescence, it was found that the microenvironment around the residues of Tyr and Trp of BSA had no significant change after binding to BRT. FT-IR and molecular docking studies confirmed that the secondary structure of protein changed during the complexation of BRT with BSA. Experimental results showed that the addition of some metal ions (Ca2+, Zn2+, Cu2+ and Co2+) significantly increased the binding interaction of BRT with BSA. This study is helpful to further evaluate the pharmacological characteristics of BRT and provides an important reference for the design of new drugs.