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

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_b) of 10⁴ M^-1 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⁺, Cu²⁺, Ca²⁺, Mg²⁺, Ni²⁺, Fe³⁺, and Co²⁺, are detrimental to the binding of palbociclib to HAG, with the exception of Zn²⁺, which is favorable.