Department of Chemistry, IAU, Central Tehran Branch (IAUCTB), Tehran, Iran.
Department of Chemistry, IAU, Central Tehran Branch (IAUCTB), Tehran, Iran; Department of Dermatology, University of California, San Francisco, CA, USA.
J Photochem Photobiol B. 2015 Jul;148:31-36. doi: 10.1016/j.jphotobiol.2015.03.001. Epub 2015 Apr 1.
Arsenic trioxide (ATO) also known as Trisenox, is an anticancer chemotherapeutic drug which has been used in treating diagnosed and relapsed patients with acute promyelocytic leukemia (APL). Serum albumin is the most abundant of the proteins in blood plasma and is the major transporter for delivering several drugs in vivo. The current study was designed to evaluate the potential ability of human and bovine serum albumin for delivering arsenic trioxide. Therefore, interaction of arsenic trioxide with HSA and BSA was investigated in aqueous solution at physiological conditions using a constant protein concentration and various drug contents. FTIR and UV-Vis spectroscopic methods were used to analyze arsenic trioxide and protein binding modes, the binding constants and the effect of drug complexation on HSA and BSA stability and conformation. Results of this study showed that drug complexation altered protein conformation by major reduction of α-helix and increase of turn structure which is indicative of a partial protein destabilization. Structural analysis revealed that arsenic trioxide bind HSA and BSA with overall binding constants of KATO-HSA=1.07 (±0.01)×10(4) M(-1) and KATO-BSA=1.27(±0.02)×10(4) M(-1). It could be concluded that serum albumins can be considered as good carriers for delivering arsenic trioxide to target tissue.
三氧化二砷（ATO），又名 Trisenox，是一种抗癌化疗药物，已用于治疗确诊和复发的急性早幼粒细胞白血病（APL）患者。血清白蛋白是血浆中最丰富的蛋白质，是体内输送多种药物的主要载体。本研究旨在评估人血清白蛋白和牛血清白蛋白输送三氧化二砷的潜在能力。因此，在生理条件下，使用恒定的蛋白质浓度和不同的药物含量，在水溶液中研究了三氧化二砷与人血清白蛋白和牛血清白蛋白的相互作用。采用傅里叶变换红外光谱（FTIR）和紫外可见光谱（UV-Vis）光谱法分析了三氧化二砷与蛋白质的结合模式、结合常数以及药物络合对 HSA 和 BSA 稳定性和构象的影响。研究结果表明，药物络合通过主要减少α-螺旋和增加转角结构来改变蛋白质构象，这表明蛋白质部分失稳。结构分析表明，三氧化二砷与人血清白蛋白和牛血清白蛋白的结合常数分别为 KATO-HSA=1.07(±0.01)×10(4) M(-1)和 KATO-BSA=1.27(±0.02)×10(4) M(-1)。可以得出结论，血清白蛋白可以被认为是将三氧化二砷输送到靶组织的良好载体。
