三磷酸腺苷二钠和金属离子对洛索洛芬钠与牛血清白蛋白结合的影响

The Influence of Adenosine 5’-triphosphate Disodium Salt and Metal Ions on the Binding of Loxoprofen Sodium to Bovine Serum Albumin

药品滥用是一个严峻的社会问题,对公众的健康和安全构成重大威胁.牛血清白蛋白(BSA)作为备受青睐的模型蛋白,常被用于研究药物与蛋白质的结合特性,这类研究有助于深入了解药物在生物体内的运输、分布及代谢过程.通过应用不同的光谱和计算技术,评估了三磷酸腺苷二钠(Na2ATP)和金属离子对洛索洛芬钠(LOXNa)与牛血清白蛋白的结合性能.多光谱和分子对接方法表明,Na2ATP和LOXNa通过静态猝灭机制形成的基态配合物在Sudlow位点Ⅱ的ⅢA子域的疏水腔中相互作用,形成1个结合位点.其结合常数为~10~3mol/L且两种药物在结合过程中展现出正协同药物效应.络合是自发的(ΔG~-29 kJ/mol),并且是焓驱动的(ΔH~82.16 kJ/mol和ΔS~365 J/(mol·K)),主要通过疏水作用力介导.同步荧光光谱数据表明,Na2ATP-LOXNa与BSA的相互作用显著改变了BSA的二级结构构象,特别是对酪氨酸残基的影响比对色氨酸残基的更为显著.此外,通过荧光法测定了金属离子存在时体系的结合常数和结合位点数,同时,还深入探讨了金属离子的存在对药效可能产生的影响.

Drug abuse represents a critical social issue that poses significant threats to public health and safety.As a highly favored model protein,bovine serum albumin(BSA)is frequently utilized to investigate the binding characteristics of drugs with proteins.Such investigations provide valuable insights into the transportation,distribution,and metabolism of drugs within biological systems.This study evaluated the binding properties of 5-triphosphate disodium salt(Na2ATP)and metal ions on loxoprofen sodium(LOXNa)with BSA by applying different spectroscopic and computational techniques.The multi-spectroscopic and molecular docking approaches reveal that novel Na2ATP and LOXNa also interact in subdomain IIIA of of Sudlow site II by forming ground state complexes following a static quenching mechanism.The binding constant is approximately 103 M-1,and during the binding process,these two drugs exhibit positive synergistic drug effects.The complexation is spontaneous(ΔG~-29 kJ/mol),and enthalpy-driven(ΔH~82.16 kJ/mol andΔS~365J/mol),and is primarily mediated by hydrogen bonding and van der Waal forces.Furthermore,the research revealed that the interaction between Na2ATP-LOXNa and BSA could potentially alter the drug's transportation and release behavior within the body,ultimately influencing its bioavailability and therapeutic outcomes.Additionally,the existence of metal ions could have an impact on the stability and activity of the drug,offering crucial theoretical insights for enhancing our understanding of the interaction mechanisms between drugs and biological molecules,as well as for optimizing drug design strategies.