Hu Si-Yuan, Lin Wen, Li Wen-Jie, Ding Xin, Zhao Ru-Fang, Hu Yan-Jun
Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, College of Chemistry and Chemical Engineering, Hubei Normal University, Huangshi, 435002, PR China.
Anal Bioanal Chem. 2025 Jan;417(2):251-263. doi: 10.1007/s00216-024-05665-3. Epub 2024 Nov 22.
This study investigated the molecular mechanisms of the interactions between three antitumor active monosaccharides and human serum albumin (HSA) using spectroscopic and electrochemical analyses, supplemented by molecular docking simulations. The antitumor efficacy of these monosaccharides can be significantly enhanced by covalent drug coupling, while HSA, with its long half-life and low immunogenicity, provides new opportunities for the development of advanced antitumor drug delivery systems. The results showed that these monosaccharides effectively burst the fluorescence of HSA. Thermodynamic analysis revealed that Fucose undergoes a spontaneous, exothermic process that decreases entropy, while the binding of Mannose and Galactose is entropy-driven. Notably, the addition of these three monosaccharides slightly compacts the structure of HSA, stabilizing its transport and delivery in vivo, with the binding strength categorized as Fucose > Mannose > Galactose. These variations in binding constants explain the differences in efficacy and potential side effects in antitumor therapy. Further studies have shown that the interaction between monosaccharides and HSA improves drug stability and targeting, thereby enhancing antitumor activity. An in-depth study of these interactions may provide new insights into the design and optimization of antitumor drugs and the further development of novel antitumor therapies.
本研究采用光谱和电化学分析方法，并辅以分子对接模拟，探究了三种抗肿瘤活性单糖与人血清白蛋白（HSA）之间相互作用的分子机制。通过共价药物偶联可显著增强这些单糖的抗肿瘤疗效，而HSA具有较长的半衰期和较低的免疫原性，为先进抗肿瘤药物递送系统的开发提供了新机遇。结果表明，这些单糖能有效猝灭HSA的荧光。热力学分析显示，岩藻糖经历一个自发的放热过程，该过程熵减小，而甘露糖和半乳糖的结合是由熵驱动的。值得注意的是，添加这三种单糖会使HSA的结构略有紧凑，稳定其在体内的运输和递送，结合强度排序为岩藻糖>甘露糖>半乳糖。这些结合常数的变化解释了抗肿瘤治疗中疗效和潜在副作用的差异。进一步研究表明，单糖与HSA之间的相互作用提高了药物稳定性和靶向性，从而增强了抗肿瘤活性。对这些相互作用的深入研究可能为抗肿瘤药物的设计和优化以及新型抗肿瘤疗法的进一步发展提供新见解。
