Multispectral and molecular simulation of the interaction of human α1-acid glycoprotein with palbociclib.

Yu-Ting Wu, Dong Chen, Liang Han, Shao-Liang Jiang, Jie-Hua Shi, Li Li, Wang-Cai Chen, Jia-Ping Huang

Journal: Biochimica et biophysica acta. General subjects 2024;1868(11):130712

PMID: 39313164

Full Text on Elsevier Science View on PubMed

Abstract

Palbociclib, a selective CDK4/6 inhibitor with potent anti-tumor effects, was investigated for its interaction with human α1-acid glycoprotein (HAG). Spectral analysis revealed that palbociclib forms a ground state complex with HAG, exhibiting binding constant (K) of 10 M at the used temperature range. The interaction between the two was determined to be driven mainly by hydrogen bonding and hydrophobic forces. Multispectral studies indicated that the bound palbociclib altered the secondary structure of HAG and reduced polarity around Trp and Tyr amino acids. And, molecular docking and dynamics simulations verified the experimental findings. Finally, most of the metal ions present in plasma, such as K, Cu, Ca, Mg, Ni, Fe, and Co, are detrimental to the binding of palbociclib to HAG, with the exception of Zn, which is favorable.

Address: College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: [email protected].; College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China.; College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: [email protected].

DOI: 10.1016/j.bbagen.2024.130712

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MeSH Terms: Humans, Pyridines, Piperazines, Orosomucoid, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Binding, Hydrogen Bonding, Hydrophobic and Hydrophilic Interactions, Binding Sites