基于头孢曲松钠–牛血清白蛋白相互作用机制的药物协同性研究

Study on Drug Synergy Based on the Interaction Mechanism between Ceftriaxone Sodium and Bovine Serum Albumin

摘要: 本文采用荧光和同步荧光光谱法，基于头孢曲松钠(CRO)–牛血清白蛋白(BSA)相互作用机制研究药物协同性和CRO蛋白结合率及BSA中酪氨酸(Tyr)和色氨酸(Trp)残基的药物结合率。结果表明：CRO与BSA结合使BSA中Tyr和Trp残基的荧光发生静态荧光猝灭，且均参与体系结合反应。N_{SFQ (Tyr)} > N_{SFQ (Trp)}，结合位置更靠近Tyr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 ≈ 1，当4.08 mg/L < c_CRO < 8.16 mg/L时，CRO-BSA中Tyr残基的药物结合率W(Q)为6.5%~12.6%，Trp残基的药物结合率W(Q)为6.35%~12.07%，Tyr和Trp残基的药物结合对CRO的药效基本没有影响，CRO的蛋白结合率可达95%以上。

Abstract: In this paper, we used fluorescence and synchronous fluorescence spectroscopy to study drug synergism and CRO protein binding and drug binding of tyrosine (Tyr) and tryptophan (Trp) residues in BSA based on the mechanism of ceftriaxone sodium (CRO)-bovine serum albumin (BSA) interaction. The results showed that CRO binding to BSA caused static fluorescence burst of Tyr and Trp residues in BSA, and both were involved in the system binding reaction. N_{SFQ (Tyr)} > N_{SFQ (Trp)}, the binding position was closer to the Tyr residue, the number of binding sites n ≈ 1, ΔG < 0, ΔH > 0, ΔS > 0, and the system environment was predominantly hydrophobic; under simulated physiological conditions, the Hill coefficient n_H ≈ 1, when 4.08 mg/L < c_CRO < 8.16 mg/L, the drug binding rate W(Q) of Tyr residues in CRO-BSA was 6.5%~12.6%, and that of Trp residues was 6.35%~12.07%, and the drug binding of Tyr and Trp residues was basically unaffected by the drug efficacy of CRO. The protein binding rate of CRO could reach more than 95%.