Investigating the Effect of Tyrosine Kinase Inhibitors on the Interaction between Human Serum Albumin by Atomic Force Microscopy

Yuna Fu; Jianhua Wang; Yan Wang; Heng Sun

doi:10.3390/biom12060819

Investigating the Effect of Tyrosine Kinase Inhibitors on the Interaction between Human Serum Albumin by Atomic Force Microscopy

Biomolecules. 2022 Jun 11;12(6):819. doi: 10.3390/biom12060819.

Authors

Yuna Fu¹, Jianhua Wang¹, Yan Wang², Heng Sun¹

Affiliations

¹ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
² Key Laboratory of Drug Design, College of Chemistry and Chemical Engineering, Huangshan University, Huangshan 245041, China.

Abstract

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 F_i and the non-specific interaction force F₀ between HSA pairs was analyzed. Based on the force measurements, F_i and F₀ between HSA pairs in the control experiment were calculated to be 47 ± 1.5 and 116.1 ± 1.3 pN. However, F_i was significantly decreased in TKIs, while F₀ 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.

Keywords: atomic force microscopy; human serum albumin; protein–protein interactions; tyrosine kinase inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dasatinib / pharmacology
Humans
Microscopy, Atomic Force
Molecular Docking Simulation
Protein Kinase Inhibitors* / chemistry
Protein Kinase Inhibitors* / pharmacology
Serum Albumin, Human*

Substances

Protein Kinase Inhibitors
Dasatinib
Serum Albumin, Human

Grants and funding

This research was funded by [the National Major Scientific Research Instrument Development Project of NSFC] grant number [21827812], and [the Natural Science Research Program of Huangshan University] grant number [2020xkjq018].