肽超分子自组装:结构调控和功能化

生物分子自组装对生物体有重要意义,利用生物分子构筑具有功能性的有序组装体一直是人们关注的焦点.肽分子是一类重要的组装基元,肽的超分子自组装可形成多种纳米或微米尺度的结构,并可应用于能源、医药等领域.如何实现肽自组装结构的精准调控以及精准调控肽自组装实现功能化,是目前该领域面临的新挑战.肽的自组装是基于非共价键力的协同作用实现的,通过各种因素调节这些非共价键力的作用,是实现自组装结构调控和功能化的关键.虽然自组装结构调控可以通过改变外部环境调控,但是通过精确分子设计、组装基元分子间的相互作用调控可以更好地实现结构的精准调控;并有利于进一步通过引入功能性分子作为组装基元,实现自组装体的功能化.本文将针对肽自组装体的结构调控以及功能化两个方面对相关研究进行综述.     

二苯丙氨酸二肽微纳米结构的可控组装及应用

近年来,生物组装单元构筑微纳米结构的组装体在生物纳米技术等领域得到了广泛的研究。不同形貌的微纳米组装体可以通过生物分子的自组装这样快速、简便的方法获得。在众多肽基构筑基元中,二苯丙氨酸二肽及其衍生物作为一种生物活性的肽,具有生物兼容性好、容易化学修饰/生物功能化、制备简单等特点,是构筑微纳米结构材料时重要的生物基元之一。通过可控的方法组装,可以得到基于二苯丙氨酸及其衍生物的不同结构的组装体,他们在光学、机械工程、电化学传感检测等方面也具有广阔的应用前景。研究证明通过改变组装条件以及引入外源小分子等方法可以实现调控短肽的分子组装。本文综述了二苯丙氨酸二肽微纳米组装体的可控组装及他们在生物医学、生物传感、光电材料、光波导和催化等方面的应用。     

界面超分子化学与响应性功能表面

超分子化学和界面的结合有效地促进了超分子化学和胶体与界面科学的发展。刺激响应性超分子界面,因在外界刺激作用下能够引起界面物理化学性质的改变并带来新的界面功能,而受到广泛的关注。近年来,溶液中基于偶氮苯 环糊精主客体相互作用的超分子组装体已经得到了广泛的研究。我们将溶液中基于偶氮苯环糊精主客体作用的可控可逆超分子组装体转移到界面上,构筑了具有刺激响应性的功能化超分子界面,并实现了表面浸润性的可逆调控、生物大分子的可控吸附与脱附、光可控的生物电化学催化等功能。我们期待类似的概念可以拓展到其他超分子体系,构筑具有特定结构的功能界面。     

超分子聚集体构筑单元的分子设计及其自组装研究进展

超分子聚集体因有着丰富的形貌和多样化的功能,并具有良好的可调控性,而备受广大超分子科学家的关注。不同结构的超分子聚集体在新材料开发、药物传输、生物成像和医疗卫生等领域均有着极其重要的研究价值和应用前景。基于在不同领域中超分子聚集体的应用特点,其自组装构筑单元的设计方法也有着诸多的选择,如何高效地设计并制备有价值的超分子体系构筑单元已经成为超分子化学研究的一个重要课题。基于超分子聚集体自组装过程的影响因素,对超分子聚集体构筑单元的主要设计方法和思路进行了总结和分析,为后续不同体系超分子聚集体构筑单元的设计及其自组装过程的相关研究提供重要的参考。     

稀土超分子配合物研究进展

超分子化学作为"广义上的配位化学",是一个充满活力的领域.基于配位自组装,设计合成具有不同拓扑结构和功能特性的超分子配合物是超分子化学的研究重点.基于稀土元素构筑的超分子配合物不仅丰富了配位超分子体系,也是制备功能性配合物的核心内容.主要从拓扑结构调控、结构修饰和功能特性等方面综述了螺旋、格子、环状和笼状等稀土超分子配...     

可控分子组装的自驱动胶体马达及其生物医学应用

人造胶体马达是能够将不同形式的能量转化为流体中机械运动的微纳米机器.自2 0 1 2年以来,将自下而上的可控分子组装与自上而下的方法有效结合已成为可控构筑胶体马达的重要策略之一.基于可控分子组装(如层层组装)的胶体马达具有易于实现规模化制备、能够对外界刺激作出响应、便于实现多功能化等优点.本文综述了通过将各种功能性构筑基元集成到组装结构中进而实现胶体马达的可控构筑、运动控制以及生物医学应用等方面的研究进展.主要介绍了基于不同层层组装结构的气泡驱动马达的可控构筑,基于聚电解质多层膜微胶囊及纳米管的近红外光驱动马达的构筑,生物界面化马达的制备,实现对胶体马达运动速度、方向及状态有效控制的主要方法,以及马达在药物靶向递送、光热治疗和生物毒素清除等生物医学领域中的应用.     

人工分子机器:分子尺度运动的精准化与可视化

分子机器在自然界至关重要,其在生物过程中执行了大量复杂的功能,从而实现不同尺度的动态行为调控.受生物系统的启发,科学家致力于研究人工分子机器在分子尺度下的精准构筑和定向运动,并通过层级组装实现信号传递和功能放大,从而推动动态智能材料的设计发展.但如何利用新方法精准构筑复杂的人工分子机器,如何将分子尺度的运动动态进行“可视化”,以及如何在生命科学研究中发挥其功能,一直是分子机器领域的研究热点.本文基于本课题组的工作,系统介绍了人工分子机器在分子尺度的精准结构构筑、信号输出以及其在跨膜运输方面的研究.最后总结了该领域在多尺度精细化和功能化方面的挑战,并展望了分子机器在宏观智能材料领域的发展前景.     

有机阳离子-无机多阴离子复合物:高分子体系中的组装及其自组装

有机阳离子包覆多金属氧簇无机多阴离子形成的具有确定化学组成、两亲性核壳结构超分子复合物,具有易于调控和集成有机和无机组分结构与功能的特性.以此类复合物为预组装体的自组装和高分子功能杂化材料展现了一类具有多方面构筑超分子组装体的新型构筑基元体系.如何实现预组装体复合物在结构稳定、具有良好加工性基材中的组装和功能化成为这一领域的重要研究内容.本文系统地总结了基于此类超分子复合物的高分子纳米复合材料和溶液中组装方面的研究进展与发展趋势.     

聚合物复合物层层组装膜

层层组装是一种基于物质交替沉积而制备复合膜的方法,可以实现膜的结构和组成的精确调控.聚合物复合物是基于各种分子间弱相互作用力而形成的超分子聚集体,其种类包括聚阳离子-聚阴离子复合物、聚电解质-有机小分子复合物、中性聚合物-聚合物复合物以及聚合物-无机杂化复合物等.在本文中,以作者的研究结果为基础,阐明聚合物复合物的层层组装是一种方便、快捷的功能复合膜的构筑方法,具有如下优点:(1)聚合物复合物大的尺度可以实现聚合物复合物层层组装膜的快速构筑;(2)聚合物复合物的结构在组装溶液中和成膜后都容易调控,方便聚合物复合物层层组装膜结构的精细调控.(3)聚合物复合物层层组装膜可以构筑非复合的聚合物层层组装所不能获得的膜结构及功能.     

超两亲分子:可控组装与解组装

与基于共价键的两亲性分子相对照,超两亲分子系指基于非共价键构筑的两亲分子.基于超分子体系的分子工程学的思想,本文总结了超两亲分子的各种类型,包括小分子型、聚合物型和响应性超两亲分子等,以及组装超两亲分子的各种推动力,如主客体相互作用、基于电荷转移作用和不同分子间的协同作用等.研究表明,超两亲分子的研究既可丰富传统的胶体界面化学,又为高级结构的可控组装提供了新的构筑基元,并为制备功能超分子材料开拓了新的途径.     

Research Progress of Regulation of Driving Forces in Short Peptide Supramolecular Self-Assembly北大核心CSCD

Some short peptides can spontaneously self-assemble into various nanostructures via the synergistic driving forces of non-covalent interactions. These non-covalent interactions,including electrostatic interaction,hydrogen bonding,aromatic interactions and other non-covalent interactions,are usually highly coupled together. Through rational sequence design and proper modification of short peptide molecules,the driving forces could be regulated purposively,and the nanostructures and morphologies of the self-assemblies could be controlled accordingly,and thus so as to achieve the fabrication of peptide-based supramolecular biomaterials and develop their functions. In this paper,the effects of hydrogen bonding,π-π stacking, electrostatic interaction,hydrophobic interaction,metal ion coordination and chiral center on the self-assembly behavior of peptide self-assembly have been reviewed. The driving force regulation strategies, including sequence design,pH and concentration adjustment and metal ion coordination,and the resulted nanostructures have also been discussed. We also make the outlooks on the development of peptide-based supramolecular biomaterials with specific functions in biomedicines and biocatalysis. © 2022, Science Press (China). All rights reserved.     

Macroscopic Supramolecular Assembly and Its Applications

Macroscopic supramolecular assembly (MSA) has been a recent progress in supramolecular chemistry.MSA mainly focuses on studies of the building blocks with a size beyond ten micrometers and the non-covalent interactions between these interactive building blocks to form ordered structures.MSA is essential to realize the concept of"self-assembly at all scales" by bridging most supramolecular researches at molecular level and at macroscopic scale.This review summaries the development of MSA,the basic design principle and related strategies to achieve MSA and potential applications.Correspondingly,we try to elucidate the correlations and differences between "macroscopic assembly" and MSA based on intermolecular interactions;the design principle and the underlying assembly mechanism of MSA are proposed to understand the reported MSA behaviors;to demonstrate further applications of MSA,we introduce some methods to improve the ordered degree of the assembled structures from the point of precise assembly and thus envision some possible fields for the use of MSA.     

Peptide-Based Optical/Electronic Materials: Assembly and Recent Applications in Biomedicine,Sensing, and Energy Storage

The unique optical and electronic properties of living systems are impressive. Peptide-based supramolecular self-assembly systems attempt to mimic these properties by preparation optical/electronic function materials with specific structure through simple building blocks, rational molecular design, and specific kinetic stimulation. From the perspective of building blocks and assembly strategies, the unique optical and electronic properties of peptide-based nanostructures, including peptides self-assembly and peptides regulate the assembly of external function subunits, are systematically reviewed. Additionally, their applications in biomedicine, sensing, and energy storage are also highlighted. This bioinspired peptide-based function material is one of the hot candidates for the new generation of green intellect materials, with many advantages such as biocompatibility, environmental friendliness, and adjustable morphology.     

基于两亲性喹喔啉的超分子凝胶：手性信号反转以及多重响应手性光学开关

The regulation of supramolecular chirality has applications in various aspects including asymmetric catalysis, chiral sensing, optical materials and smart devices. Additionally, it provides opportunities for the simulation of important activities in living organisms and the clarification of their mechanisms. Herein, we synthesized a chiral gelator SQLG (styrylquinoxalinyl L-amino glutamic diamide) containing a π-conjugated headgroup by introducing the quinoxaline-derived moiety into L-glutamic diamide-based amphiphile via two simple condensation steps. SQLG self-assembled into nanofibers through multiple intermolecular interactions, including π–π stacking, hydrogen bonding and van der Waals interaction, leading to gelation of various organic solvents ranging from nonpolar to polar ones. Chirality transfer from the chiral center to the supramolecular level was observed when organogels formed, which manifested itself in circular dichroism (CD) spectra. The organogels formed in polar solvents such as N, N-dimethylformamide (DMF) and nonpolar solvents such as toluene exhibited opposite signals of supramolecular chirality, attributed to different hydrogen bonding strengths and thus two different types of gelator stacking modes of the gelators which was confirmed by infrared spectroscopy (IR) and X-ray diffraction (XRD). Circular polarized luminescence (CPL) denotes left-handed or right-handed circularly polarized light with different intensities emitted by the chiral luminescent system, and it characterizes the chirality of the excited state, which finds potential application in fields such as 3D optical displays, optical data storage, polarization-based information encryption and bioencoding. Owing to the strong fluorescence and supramolecular chirality, the toluene gel emitted right-handed circular polarized luminescence upon excitation, while the gel formed in DMF did not exhibit CPL emission because of its relatively weak fluorescence. Furthermore, the organogels responded rapidly and distinctly to the stimulus of acid due to the proton-accepting sites in the quinoxaline skeleton. Utilizing NMR spectroscopy, we found that the two nitrogen atoms in the quinoxaline moiety could be protonated upon acidification. During the process, intramolecular charge transfer (ICT) was significantly strengthened and the driving forces of self-assembly underwent remarkable changes, resulting in the collapse of the yellow transparent organogel into a red dispersion. Meanwhile, transformation from nanofibers to nanospheres was observed using a scanning electron microscope (SEM). With change in stacking modes in the supramolecular assembly, a complete inversion of the CD signal was detected. The CPL signal was found to be switched off, which along with the other changes of the system could subsequently be recovered by neutralization of the entire system. Therefore, we constructed a chiroptical switch with multiple stimuli-responsiveness through the introduction of an acid-sensitive π-conjugated moiety into the L-glutamic diamide-based chiral amphiphile.     

异氰酸苯酯诱导的类胶原多肽自组装

Synthetic matrices provide powerful tools for dissecting molecular interactions involved in the organization of the extracellular matrix (ECM), establishment of cell axis polarity, and suppression of neoplasticity in pre-cancerous endothelial cells. Collagen is the most abundant protein in extracellular matrix. A de novo approach is essential for the synthesis of collagen matrices which can have a broad impact on the understanding of matrix biology and our capacity to construct safe and medically useful biomaterials. Conventionally, the ECM has been studied by an analytical "top-down" approach, where the individual components of the matrix are first isolated and then characterized to explore their biochemical and functional properties. Since native collagen is difficult to modify and can engender pathogenic and immunological side effects, its application on tissue regeneration is limited. Therefore, we attempted to synthesize artificial collagen directly through small organic molecule recognition. The collagen-like peptides possess various benefits such as being clean, programmable, and easy to modify; therefore, in recent years, they have been used as ideal substrates for the synthesis of collagen nanomaterials. The self-assembly of collagen-like peptides is mainly driven by various non-covalent interactions such as electrostatic attraction, π-π stacking, and metal coordination. This renders a difficulty in the rational design of uniform nanostructures from short synthesized peptides and demands a novel strategy. To date, small organic molecules have been rarely used for the self-assembly of collagen-like peptides. In the present study, we attempted to use the small organic molecules for the combined supramolecular self-assembly of collagen-like peptides. Initially, the collagen-like peptides, (POG)₆ and (POG)₈, synthesized by the solid-phase synthesis technique, were both modified chemically using 4, 4'-methylene bis(phenyl isocyanate) to obtain the collagen-like hybrid peptides, AP₆ and AP₈, respectively. Phenyl isocyanate contributes to the formation of potential weak forces, such as hydrogen bonds and π-π stacking at the N-terminal regions of the collagen-like hybrid peptides. The purity and molecular weight of the collagen-like hybrid peptides were analyzed using analytical high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization time of flight (MALDI-TOF), respectively. The stability of AP₆ and AP₈ triple helices was analyzed by circular dichroism (CD) spectroscopy. The small organic molecule 4, 4'-methylene bis(phenyl isocyanate) promoted the unfolding of (POG)₆ and increased the melting temperature (T_m) of (POG)₈ from 37.7 to 58.8 ℃to form a triple helix. The hydrodynamic radii of collagen-like hybrid peptides were measured by dynamic light scattering (DLS). Atomic force microscopy (AFM) and transmission electron microscopy (TEM) were used to analyze the morphology of the aggregation states. AFM results showed that the collagen-like hybrid peptides, AP₆ and AP₈, formed nanofibers spontaneously. Consistent with the AFM results, TEM showed that the AP₆ and AP₈ collagen-like hybrid peptides also formed nanofiber structures. The formation of stable complexes was attributed to the presence of multiple weak interactions such as hydrogen bonding, π-π stacking, and hydrophobic interactions. In the present study, we demonstrated that the chemical modification of collagen-like polypeptides at the N-terminus via the small organic molecule, 4, 4'-methylene bis(phenyl isocyanate), promoted the intramolecular and intermolecular assembly of collagen-like peptides. A simple and effective strategy has been developed in this study to promote the self-assembly of collagen-like peptides.     

Orthogonal Halogen‐Bonding‐Driven 3D Supramolecular Assembly of Right‐Handed Synthetic Helical Peptides

Peptide‐mediated self‐assembly is a prevalent method for creating highly ordered supramolecular architectures. Herein, we report the first example of orthogonal C?X???X?C/C?X???π halogen bonding and hydrogen bonding driven crystalline architectures based on synthetic helical peptides bearing hybrids of l ‐sulfono‐γ‐AApeptides and natural amino acids. The combination of halogen bonding, intra‐/intermolecular hydrogen bonding, and intermolecular hydrophobic interactions enabled novel 3D supramolecular assembly. The orthogonal halogen bonding in the supramolecular architecture exerts a novel mechanism for the self‐assembly of synthetic peptide foldamers and gives new insights into molecular recognition, supramolecular design, and rational design of biomimetic structures.     

超分子相互作用主导的纳米药物成核

纳米沉淀法是目前制备纳米药物的主要途径, 是指通过向药物的良溶剂中引入不良溶剂产生过饱和体系, 进而形成纳米尺度药物颗粒的方法. 该方法操控灵活, 能够大范围地选择药物分子、 溶剂、 载体、 表面活性剂及其它赋形剂, 实现对纳米药物成核及生长过程的调控. π-π堆积和疏水相互作用等分子间弱相互作用能够主导纳米药物成核, 从而用于制备高生物安全性的无载体纳米药物(CFNs). 目前超分子自组装在成核过程中的具体作用、 协同效应及调控方法尚缺少归纳总结. 根据纳米沉淀法的成核理论, 本文对超分子相互作用在成核过程中的重要贡献进行了诠释; 基于目前单药自组装CFNs的进展, 对多药共组装CFNs的优势进行了强调; 并将超分子相互作用主导成核的概念拓展到通过金属离子螯合形成的CFNs. 从理论上阐明了超分子相互作用在纳米药物成核过程中的主导作用, 将极大促进以高生物安全、 多功能及以联合治疗为标志的下一代CFNs的发展.     

Supramolecular colloidal motors via chemical self-assembly

A colloidal motor can convert energy stored in the environment to achieve mechanical motion and exhibit dynamic behaviors in fluids. To overcome the challenges presented to a colloidal motor, controlled molecular self-assembly technology provides new opportunities for the precise fabrication of various nanoarchitectures and facilitates fundamental research on rational design, multifunctionalization, propulsion, and controlled movement of colloidal motors. These molecular assembled colloidal motors, also called supramolecular colloidal motors, can perform special tasks at the micro- and nanoscale in the fields of biomedicine, nanotechnology, and environmental remediation. In this feature article, we first introduce the recent progress of controllable self-assembly of spatially asymmetric supramolecular colloidal motors with variable sizes, structures, and functions and discuss the relationship between structure and propulsion. Next, we review the research progress of this type of colloidal motors in biomedical and environmental fields. Finally, we propose the challenges of the supramolecular colloidal motors and future development direction.     

微凝胶胶体晶体研究进展

Poly(N-isopropylacrylamide)(PNIPAM)微凝胶粒子是一种软的胶体粒子.和单分散的SiO_2、PS、PMMA等硬的胶体粒子一样,单分散的PNIPAM微凝胶粒子也可以自组装成为高度有序的胶体晶体.微凝胶粒子软物质的特性及其对外部刺激的响应性赋予其不同于硬球的组装行为.微凝胶胶体晶体的高度有序结构及其刺激响应性使其在诸多领域有重要用途.本文分别介绍了三维及二维微凝胶胶体晶体组装的研究进展,并对已开发的基于微凝胶胶体晶体的应用进行了总结.     

Physical mechanisms and biological significance of supramolecular protein self-assembly

In living cells, chemical reactions of metabolism, information processing, growth and development are organized in a complex network of interactions. At least in part, the organization of this network is accomplished as a result of physical assembly by supramolecular scaffolds. Indeed, most proteins function in cells within the context of multimeric or supramolecular assemblies. With the increasing availability of atomic structures and molecular thermodynamics, it is possible to recast the problem of non-covalent molecular self-assembly from a unified perspective of structural thermodynamics and kinetics. Here, we present a generalized theory of self-assembly based on Wegner's kinetic model and use it to delineate three physical mechanisms of self-assembly: as limited by association of assembly units (nucleation), by association of monomers (isodesmic), and by conformational reorganization of monomers that is coupled to assembly (conformational). Thus, we discuss actin, tubulin, clathrin, and the capsid of icosahedral cowpea chlorotic mottle virus with respect to assembly of architectural scaffolds that perform largely mechanical functions, and pyruvate dehydrogenase, and RING domain proteins PML, arenaviral Z, and BRCA1:BARD1 with regard to assembly of supramolecular enzymes with metabolic and chemically directive functions. In addition to the biological functions made possible by supramolecular self-assembly, such as mesoscale mechanics of architectural scaffolds and metabolic coupling of supramolecular enzymes, we show that the physical mechanisms of self-assembly and their structural bases are biologically significant as well, having regulatory roles in both formation and function of the assembled structures in health and disease.