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

IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Shao-Liang Jiang , Yu-Ting Wu , Wang-Cai Chen , Jia-Ping Huang , Dong Chen , Li Li , Liang Han , Jie-Hua Shi
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引用次数: 0

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 (Kb) 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.
人类α1-酸性糖蛋白与帕博西尼相互作用的多光谱和分子模拟。
帕博西尼(Palbociclib)是一种选择性CDK4/6抑制剂,具有很强的抗肿瘤作用,研究人员考察了它与人类α1-酸糖蛋白(HAG)的相互作用。光谱分析显示,palbociclib 与 HAG 形成基态复合物,在所用温度范围内的结合常数(Kb)为 104 M-1。二者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,结合后的帕博西尼改变了 HAG 的二级结构,降低了 Trp 和 Tyr 氨基酸周围的极性。分子对接和动力学模拟也验证了实验结果。最后,血浆中存在的大多数金属离子,如 K+、Cu2+、Ca2+、Mg2+、Ni2+、Fe3+ 和 Co2+,都不利于 palbociclib 与 HAG 的结合,只有 Zn2+ 有利。
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来源期刊
Biochimica et biophysica acta. General subjects
Biochimica et biophysica acta. General subjects 生物-生化与分子生物学
CiteScore
6.40
自引率
0.00%
发文量
139
审稿时长
30 days
期刊介绍: BBA General Subjects accepts for submission either original, hypothesis-driven studies or reviews covering subjects in biochemistry and biophysics that are considered to have general interest for a wide audience. Manuscripts with interdisciplinary approaches are especially encouraged.
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