非共价相互作用增加紫杉醇溶解度的寡肽研究
An oligopeptide improves solubility of paclitaxel by non-covalent interaction
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摘要:
本文基于寡肽与紫杉醇 (paclitaxel, PTX) 的非共价键相互作用促进PTX溶解的原理, 设计了寡肽分子 (N terminal-W(L)-FFGREKD-C terminal, W8), 并通过实验检测了W8对PTX的增溶效果。根据PTX的结构特点, 设计了PTX的增溶寡肽分子W8, 使用分子对接程序考察了W8-PTX的结合效果以及可能的最优结合构象; 采用反相高效液相色谱法对W8的增溶效果进行检测, 并从分子水平对增溶原理进行讨论。对接结果显示, W8和PTX之间有两对π-π相互作用和数个氢键相互作用; 实验结果表明, W8对PTX增溶作用明显, PTX在水中的溶解度比其饱和溶解度提高了28倍。本研究为进一步优化设计增溶PTX的寡肽奠定了基础, 为设计更安全的寡肽型增溶辅料提供了思路。
Abstract:Based on the principle of non-covalent interactions between oligopeptides and paclitaxel for improving the solubility of paclitaxel, an oligopeptide, N terminal-W(L)-FFGREKD-C terminal (W8), was designed and the solubilization effect of W8 on paclitaxel was detected through experiments. The binding efficiency and the possible optimal conformation were optimized by molecular docking program. The solubilization effect of W8 on paclitaxel was determined by RP-HPLC. And the solubilization mechanism of oligopeptide to paclitaxel was proposed at molecular level. It was indicated from the docking result that there existed π-π interactions and several hydrogen-bond interactions between the oligopeptide and paclitaxel. After being solubilized by the oligopeptide, the aqueous solubility of paclitaxel was increased to 28 times. This study provided basis for further research of the solubilization of paclitaxel by oligopeptide and confirmed a novel approach for the design of safe oligopeptide solubilizing excipient.
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