College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China.
College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China.
Biochim Biophys Acta Gen Subj. 2024 Nov;1868(11):130712. doi: 10.1016/j.bbagen.2024.130712. Epub 2024 Sep 21.
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.
帕博西尼，一种选择性细胞周期蛋白依赖性激酶 4/6 抑制剂，具有强大的抗肿瘤作用，其与人血清白蛋白（HAG）的相互作用受到了研究。光谱分析表明，帕博西尼与 HAG 形成了基态复合物，在所用温度范围内的结合常数（K）为 10 M。两种物质之间的相互作用主要由氢键和疏水作用力驱动。多光谱研究表明，结合的帕博西尼改变了 HAG 的二级结构，并降低了色氨酸和酪氨酸氨基酸周围的极性。并且，分子对接和动力学模拟验证了实验结果。最后，除了锌以外，血浆中存在的大多数金属离子，如 K、Cu、Ca、Mg、Ni、Fe 和 Co，都不利于帕博西尼与 HAG 的结合。
