蟾毒配基类成分与人血清白蛋白结合的荧光光谱研究
首发时间:2012-12-27
摘要:研究9中蟾毒配基类成分与人血清白蛋白(HSA)亲和力的关系。在生理pH条件下,采用荧光光谱法,通过不同浓度药物对人血清白蛋白色氨酸荧光的猝灭,计算其结合常数和热力学参数。结果表明,蟾毒配基类成分使人血清白蛋白发生内源型荧光猝灭,属于静态猝灭机制;通过范特霍夫方程计算热力学常数焓变和熵变以及分子对接结果表明,氢键是影响蟾毒配基类成分与HSA发生相互作用的关键作用力。通过双波长方程计算9中蟾酥甾烯类成分与HSA间的结合常数。蟾毒配基结构中羟基越多,与HSA间的亲和力越高;结构中羟基数目相同情况下,C-11位有羟基者,结合能力最高,但当C-11位羟基旁边有羰基,结合力减小;C-16位羟基对其亲和力影响不大,但当C-16位羟基被乙酰基取代后,结合力增加;结构中有醛基存在时,结合力也随之增加。因此,蟾毒配基结构中取代基团的不同,对其与白蛋白的结合有较大影响。
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Molecular property-affinity relationship of bufadienolides and HSA in vitro
Abstract:The relationship between the structural properties of bufadienolides and their affinities for Human serum albumin (HSA) was investigated by fluorescence analysis. Fluorescence quenching data showed that the interaction of bufadienolides with HSA forms a non-fluorescent complex. The thermodynamics parameters: enthalpy change (H) and entropy change (S) were calculated via van't Hoff equation, the thermodynamics parameters data showed that the hydrogen bond was the predominant force in the binding process. The structural differences of bufadienolides influenced the binding affinity with HSA: Hydroxyl group at C-11 played a key role in the binding affinity for HSA and more OH groups in this structures could increase the binding affinity for HSA, but OH group at C16 position can hardly affect the binding affinity for HSA. Acetylation of hydroxyl groups (C16 position) improved the affinities for HSA. The presence of aldehyde also enhanced the affinities for HSA. However, C=O bond decreased the binding affinity, which provided a valuable experimental data and theoretical basis for mechanism of drug interactions.
Keywords: Bufadienolides Human serum albumin Fluorescence spectrum
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