穿膜肽Penetratin及其衍生物的解离动力学研究

项目名称： 穿膜肽Penetratin及其衍生物的解离动力学研究

项目编号： No.20873011

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 祖莉莉

作者单位： 北京师范大学

项目金额： 32万元

中文摘要： Penetratin是细胞穿透肽中极具代表性的一种，能够携带蛋白质、核酸等生物活性分子进入细胞膜中，在细胞生物学和药学等领域有着诱人的应用前景。本项目运用TOF-MS/MS多级质谱方法研究了Penetratin及其衍生物的气相碰撞诱导解离碎片，结合Penetratin解离过程中中间产物和过渡态的结构计算，推导出Penetratin气相碰撞诱导解离的动力学机理，揭示了碱性氨基酸残基在Penetratin质子化过程及肽键断裂机制中的重要作用，阐述了氢键对多肽的空间构象形成和质子转移过程的影响，为修饰Penetratin、提高其代谢稳定性和药物运输效率提供了理论依据。

中文关键词： 细胞穿膜肽；串联质谱；量子理论计算；解离动力学

英文摘要： Penetratin, a 16-residue peptide derived from the Antennapedia homeodomain in Drosophila, is one promising delivery vector for intracellular delivery of proteins and other bioactive molecules. In this project, we studied the fragmentation of penetratin and its substitutes under low energy collision-induced dissociation condition using ESI tandem mass spectroscopy and theoretical calculation. The fragmentation mechanism of penetratin and especially the contribution of the basic residues have been unravelled. Selective cleavage of the K15-K16 bond was observed for penetratin with different charges. A helix structure prevented the fragmentation of the central peptide domain and the side chain of lysine was invovled in the proton translocation process. These results may provide useful information for modifying penetratin to improve the metablic stability and cargo-delivery efficiency when using it as a potential drug delivery vector.

英文关键词： Penetratin; TOF-MS/MS; theoretical calculation; dissociation dynamics