Exploring intermolecular interaction between transporter protein, bovine serum albumin and antitumor drug Lorlatinib: Multispectral approaches combined with molecular simulation

Abstract

In this paper, the intermolecular interaction of antitumor drug loratinib (LOR) with the transporter protein, bovine serum albumin (BSA) was researched utilizing multiple spectroscopic approaches combined with molecular modeling. The experimental outcomes showed that LOR entered the hydrophobic gap between the two subintervals of BSA (site II '), formed the ground-state complex with a stoichiometric ratio of 1:1, and statically quenched the endogenous fluorescence of BSA protein. During the intermolecular interaction between the two, the binding constant was with the interval of 104-106 M−1, indicating a moderate to strong affinity between the two. In addition, there was a non-radiative energy transfer from BSA to LOR, and binding with LOR diminished the α-helix content of BSA protein and affected slightly on the microenvironment surrounding the aromatic amino acids like Trp and Tyr residues. The binding of LOR to BSA was inhibited by most common metal ions, and only the Fe3+ ion promoted it. The outcomes of experiments as well as molecular dynamics simulation showed that the primary binding forces between LOR and BSA were hydrogen bonding, hydrophobic force and van der Waals force.