基于肽类分子的多组分共组装：理性设计、多级调控与生物应用

Co-assembly of multicomponents is one of the frontiers of molecular self-assembly, due to its advantage to integrate and optimize different functionalities from the co-assembling componets. However, the design and manipulation of such self-assembling systems is much more complex than that of single component systems. In this proposal, we design the co-assembling systems based on self-assembling peptide by introducing small functional molecules or biomacromolecules as the co-assembling components. Moreover, novel control principles were exploited to self-assemble the multicomponents into hierarchically ordered functional materials with distint morphologes. In addition, biological applications based on the co-assembling materials were further assessed as well. In specific investigation: ① For small functional molecules and short peptides co-assembling system, capillary force was introduced to manipulate the hierarchical, co-assembly of components in solution phase or at interfaces, to form complex peptide micro/nanostructures. The application of co-assembling materials in the field of biosensor was further assessed. ② For biomacromolecules and short peptides co-assembling system, based on electrostatic interaction and catalytic properties, we selected polymer sugars or enzymes as the co-assembling componets. For the co-assembly of polymer sugar and peptide, we used aqeuous liquid-liquid interface to serve as the template to control the co-assembling process. As an original innovation, jet flow theroy was proposed as a feasible approcah to manipulate the co-assembling of such systems into hierarchically functional sugar-peptide materials. For the co-assembling of enzyme and peptide, metal ions were employed due to its coordination property and the allosteric effect between enzymes, so that we could fabricate hierarchical, functional metal-enzyme-peptide co-assembling materials. The applications of the co-assembled materials in the field of controlled drug release and biological catalysis were further assessed as well. The concepts, methodologies as well as results of this proposal can open an avenue for the design, manipulation and applications of molecular co-assembling systems.

多组分共组装体系的设计、调控与应用是分子自组装领域的研究前沿，也是难点之一。本项目以短肽分子为核心，设计小分子-短肽、大分子-短肽两类多组分共组装体系，从界面物理、流体力学领域获取灵感，开发新型组装调控手段，制备特定结构和功能的共组装材料，并探索其在生物化学工程领域的应用。具体研究中：①筛选不同的功能小分子，构建小分子-短肽共组装体系，利用界面毛细力实现对共组装行为的多级调控，并建立相关材料的分析传感应用体系；②基于电荷和催化活性的不同，选择多糖、酶蛋白等生物大分子，构建大分子-短肽共组装体系：以水相液液界面为模板，利用射流边界层控制液液界面处的"三传(质量、动量、热量)、一反（共组装）"，可控制备糖-肽共组装材料；利用金属配位及变构效应，合成酶-肽-金属离子三元共组装体；构建相关材料的载药缓释和生物催化应用体系。本项目研究思路、方法和成果可为分子共组装体系的设计、调控和应用提供参考。

本项目以短肽分子为核心，设计小分子-短肽、大分子-短肽两类多组分共组装体系，从界面物理、流体力学领域获取灵感，开发新型组装调控手段，制备特定结构和功能的共组装材料，并探索其在生物化学工程领域的应用。具体研究中：.1. 通过筛选不同的功能小分子以及多肽分子，构建了小分子-短肽共组装体系，利用静电相互作用、苯环堆积以及界面毛细力，实现了对多肽分子共组装行为的多级调控，获得了结构精细可控的纳米螺旋，形貌类似蒲公英的微米花结构，以及具有仿酶催化活性的多肽共组装纳米纤维，相关材料可应用于手性检测、生物催化体系，并可作为合成模板，通过仿生矿化，制备结构高度有序的无机纳米材料。.2. 基于电荷和催化活性的不同，选择多糖、酶蛋白、DNA等生物大分子， 构建了多种大分子-短肽共组装体系。以水相液液界面为模板，通过控制液液界面处的 “三传（质量、动量、热量）、一反（共组装）”，获得了薄膜、凝胶、微囊等多种糖肽复合材料；通过调控多肽、氨基酸与酶蛋白的共组装，获得了基于多肽自组装的新型整合酶体系以及水凝胶，在生物催化领域具有很好的应用特性；通过调控多肽分子与DNA的共组装，获得了非致病性且具有靶向识别特性的仿病毒纳米颗粒，可用于基因药物的靶向输运与释放。.本项目研究思路、方法和成果可为分子共组装体系的设计、调控和应用提供参考。研究成果发表在JACS（亮点文章）、Angew Chem（内封面文章）、ACS Nano、Chem Mater、Small等10余种知名学术期刊，累计发表SCI论文 27 篇，其中JCR一区论文14篇，10余篇被遴选为封面、封底或亮点文章。研究成果受到了《科技日报》、中新网、搜狐网等多家媒体的关注与报道，并作为核心内容获得了“2017年度教育部高等学校科学研究优秀成果奖自然科学二等奖” 1项。