同步荧光光谱研究头孢匹林钠与牛血清白蛋白相互作用机制

Study on the Interaction Mechanism between Cephalosporin Sodium and Bovine Serum Albumin by Synchronous Fluorescence Spectroscopy

摘要: 本文采用同步荧光光谱研究不同温度下头孢匹林钠(CP)–牛血清白蛋白(BSA)相互作用机制及药物协同性和酪氨酸(Tyr)和色氨酸(Trp)残基的药物结合率及药物的蛋白结合率。结果表明：随着CP浓度逐渐增大，波长发生红移，Tyr和Trp残基周围微环境发生改变；CP与BSA结合发生静态猝灭，Tyr和Trp残基均参与体系结合反应。N_SFQ(Tyr) < N_SFQ(Trp)，结合位置更靠近Trp残基，结合位点数n ≈ 1，ΔG < 0，ΔH > 0，ΔS > 0，体系环境以疏水作用为主；模拟生理条件下，Hill系数n_H略小于1，表现为弱的负协同作用；c_CP在48~72 μg/mL时，CP在Tyr残基的蛋白结合率W(B)为47.92%~58.00%，在Trp残基的W(B)为48.13%~65.05%时，游离药物率在40%~50%之间，表明40%~50%的药物具有药物活性，50%~65%的药物与血浆蛋白结合成结合型药物，影响药物的药理活性。

Abstract: In this paper, synchronous fluorescence spectroscopy was used to study the mechanism of cefapirin sodium (CP)-bovine serum albumin (BSA) interaction and drug synergism and the drug binding rate of tyrosine (Tyr) and tryptophan (Trp) residues as well as protein binding of the drug at different temperatures. The results showed that: with the gradual increase of CP concentration, the wavelength was red-shifted, the microenvironment around Tyr and Trp residues was changed. The binding of CP to BSA took place in a static burst, and both Tyr and Trp residues were involved in the binding reaction of the system. N_SFQ(Tyr) < N_SFQ(Trp), the binding position was closer to Trp residues, the number of binding site n ≈ 1, ΔG < 0, ΔH > 0, ΔS > 0, the system environment was dominated by hydrophobic interaction. Under simulated physiological conditions, the Hill coefficient n_H was slightly less than 1, which showed weak negative synergism. c_CP = 48~72 μg/mL, the protein binding rate of CP at Tyr residues W(B) ranged from 47.92% to 58.00%, and that at Trp residues W(B) ranged from 48.13% to 65.05%, the free drug rate ranged from 40% to 50%, indicating that 40% to 50% of the drug was pharmacologically active, and 50%~65% of the drug bound to plasma proteins to form a conjugated drug, affecting the pharmacological activity of the drug.