Investigating the Effect of Tyrosine Kinase Inhibitors on the Interaction between Human Serum Albumin by Atomic Force Microscopy
2022
Yuna Fu | Jianhua Wang | Yan Wang | Heng Sun
It is important for elucidating the regulation mechanism of life activities, as well as for the prevention, diagnosis, and drug design of diseases, to study protein–protein interactions (PPIs). Here, we investigated the interactions of human serum albumin (HSA) in the presence of tyrosine kinase inhibitors (TKIs: imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) using atomic force microscopy (AFM). The distribution of rupture events including the specific interaction force <i>F<sub>i</sub></i> and the non-specific interaction force <i>F</i><sub>0</sub> between HSA pairs was analyzed. Based on the force measurements, <i>F<sub>i</sub></i> and <i>F</i><sub>0</sub> between HSA pairs in the control experiment were calculated to be 47 ± 1.5 and 116.1 ± 1.3 pN. However, <i>F<sub>i</sub></i> was significantly decreased in TKIs, while <i>F</i><sub>0</sub> was slightly decreased. By measuring the rupture forces at various loading rates and according to the Bell equation, the kinetic parameters of the complexes were investigated in greater detail. Molecular docking was used as a complementary means by which to explore the force of this effect. The whole measurements indicated that TKIs influenced PPIs in a variety of ways, among which hydrogen bonding and hydrophobic interactions were the most important. In conclusion, these outcomes give us a better insight into the mechanisms of PPIs when there are exogenous compounds present as well as in different liquid environments.
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