糖肽超分子组装体的手性结构精确调控与功能探索

The fabrication of chiral supramolecular materials with single mirror isomers is of great research significance and one of the most important scientific issues of this major research project. As the basic building blocks of chiral materials naturally occurring, oligosaccharides and oligopeptides have been extensively applied to the preparation of chiral materials. However, oligosaccharides are currently only used as simple hydrophilic chiral substances, the manipulation mechanism of complicated saccharide rings on chirality of supramolecular materials still remains unclear. This project aims at resolving above issues, through fine-adjustment of the structure of oligosaccharides and oligopeptides for constructing supramolecular chiral materials, to achieve chirality tuning of materials and obtaining chiral isomers, even manipulating the mirror enantiomer. Preliminary results indicated that the as-prepared supramolecular chiral nanofibers assembled by basic building blocks of oligosaccharides and oligopeptides are featured by possessing single mirror isomers; the reversal of nanofibers mirror isomers can be achieved via further tune the structure of oligosaccharides and oligopeptides. We plan to further study the molecular mechanism of regulation and reversal of mirror isomers mentioned above, uncover the collaboration and competition principle of interplay of oligosaccharides and oligopeptides and further explore the potential application of chiral materials in tumor treatment.

制备具有单一镜像异构体特性的手性超分子材料具有重要研究意义，同时是本重大研究计划所最为关注的基本科学问题之一。作为自然界手性物质的基本构筑基元，寡糖与寡肽已被广泛用于手性材料的制备。但是目前寡糖仅作为简单的亲水手性物质使用，其复杂的糖环结构对于超分子材料手性调控机制不明确，寡糖之间相互作用与寡肽所参与的相互作用在手性调控过程中的协同与竞争关系不明确。本项目即针对上述问题展开，希望通过对构筑超分子手性材料的寡糖肽结构进行精细调节，以精确调控材料手性，获得单一镜像异构体，甚至对镜像对映体进行操控。初步研究结果表明，寡糖肽构筑基元自组装所形成的超分子手性纤维均有单一镜像异构特征；进一步通过精细调节寡糖肽结构，能够实现纤维镜像异构的翻转。我们计划深入研究上述镜像异构调控和翻转的分子机制，揭示其中寡糖肽相互作用的协同与竞争原理，并进一步探索手性材料在肿瘤治疗等领域的应用。

本项目发展了寡糖和寡肽协同编码单一手性超分子材料的方法。由于寡糖结构的复杂性以及其对于超分子材料手性调控的机制不明确，利用寡糖和寡肽来协同调控超分子材料的手性在超分子合成化学中极具挑战。基于糖肽组装体形成机理研究，发现寡糖和寡肽可以协同调控超分子纤维的手性、缔合行为以及生物学行为；通过糖肽分子的自组装以及共组装，实现了单一手性糖肽纤维及糖肽超螺旋结构的制备与调控。该项工作揭示了寡糖和寡肽对超分子手性的调节机制，为单一手性超分子材料的制备提供了新策略，同时为系统性理解和模拟天然手性超分子材料提供了新思路。所制备的手性材料有望应用于仿生机器人，药物传递等领域。该项工作的前期部分工作发表于J. Am. Chem. Soc., 2021, 143, 6622。文章在发表的同时被JACS spotslight以“揭示纤维缔合的秘密(Unraveling The Secrets of Fibril Associations)”为题，进行了亮点评述指出陈国颂和合作者们通过实验和理论的方法，在对纤维缔合的理解上实现了巨大跨越(great strides)。项目共发表标注SCI论文13篇，其中包括J. Am. Chem. Soc. 2篇、Acc. Chem. Res.、Adv. Mater.、Angew. Chem. Int. Ed.、CCS Chem.等。