Selective covalent capture of collagen triple helices with a minimal protecting group strategy

Collagens and their most characteristic structural unit, the triple helix, play many critical roles in living systems which drive interest in preparing mimics of them. However, application of collagen mimetic helices is limited by poor thermal stability, slow rates of folding and poor equilibrium between monomer and trimer. Covalent capture of the self-assembled triple helix can solve these problems while preserving the native three-dimensional structure critical for biological function. Covalent capture takes advantage of strategically placed lysine and glutamate (or aspartate) residues which form stabilizing charge–pair interactions in the supramolecular helix and can subsequently be converted to isopeptide amide bonds under folded, aqueous conditions. While covalent capture is powerful, charge paired residues are frequently found in natural sequences which must be preserved to maintain biological function. Here we describe a minimal protecting group strategy to allow selective covalent capture of specific charge paired residues which leaves other charged residues unaltered. We investigate a series of side chain protecting groups for lysine and glutamate in model peptides for their ability to be deprotected easily and in high yield while maintaining (1) the solubility of the peptides in water, (2) the self-assembly and stability of the triple helix, and (3) the ability to covalently capture unprotected charge pairs. Optimized conditions are then illustrated in peptides derived from Pulmonary Surfactant protein A (SP-A). These covalently captured SP-A triple helices are found to have dramatically improved rates of folding and thermal stability while maintaining unmodified lysine–glutamate pairs in addition to other unmodified chemical functionality. The approach we illustrate allows for the covalent capture of collagen-like triple helices with virtually any sequence, composition or register. This dramatically broadens the utility of the covalent capture approach to the stabilization of biomimetic triple helices and thus also improves the utility of biomimetic collagens generally.

A minimal protecting group strategy is developed to allow selective covalent capture of collagen-like triple helices. This allows stabilization of this critical fold while preserving charge–pair interactions critical for biological applications.     

Bolaform superamphiphile based on a dynamic covalent bond and its self-assembly in water

We have employed a dynamic covalent bond to fabricate a bolaform superamphiphile, which can be used as building blocks for controlled assembly and disassembly. In alkaline environment, one building block bearing a benzoic aldehyde group can react with the other building block bearing an amino group to form a bolaform superamphiphile. It is found that the bolaform superamphiphiles can self-assemble in water to form micellar aggregates. When the pH is tuned down to slightly acidic values, the benzoic imine bond can be hydrolyzed, leading to the dissociation of the superamphiphile. The micellar aggregates will also disassemble, and the loaded guest molecules are released subsequently. This line of research has enriched the family of bolaform amphiphiles, and the resulting assemblies may find application in the field of controlled and targetable drug-delivery in a biological environment.     

Protein self-assembly: technology and strategy

Proteins, as the premier building blocks in nature, exhibit extraordinary ability in life activities during which process proteins mostly self-assemble into large complexes to exert prominent functions. Inspired by this, recent chemical and biological studies mainly focus on supramolecular self-assembly of proteins into high ordered architectures, especially the assembly strategy to unravel the formation and function of protein nanostructures. In this review, we summarize the progress made in the engineering of supramolecular protein architectures according to the strategies used to control the orientation and the order of the assembly process. Furthermore, potential applications in biomedical areas of the supramolecular protein nanostructures will also be reviewed.     

Ion gels by self-assembly of a triblock copolymer in an ionic liquid

We report a new way of developing ion gels through the self-assembly of a triblock copolymer in a room-temperature ionic liquid. Transparent ion gels were achieved by gelation of a poly(styrene-block-ethylene oxide-block-styrene) (SOS) triblock copolymer in 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) with as low as 5 wt % SOS triblock copolymer. The gelation behavior, ionic conductivity, rheological properties, and microstructure of the ion gels were investigated. The ionic conductivity of the ion gels is only modestly affected by the triblock copolymer network. Its temperature dependence nearly tracks that of the bulk ionic liquid viscosity. The ion gels are thermally stable up to at least 100 degrees C and possess significant mechanical strength. The results presented here suggest that triblock copolymer gelation is a promising way to develop highly conductive ion gels and provides many advantages in terms of variety and processing.     

A novel channel-wall engineering strategy for two-dimensional cationic covalent organic frameworks: Microwave-assisted anion exchange and enhanced carbon dioxide capture

A novel channel-wall engineering strategy of the porous materials cationic covalent organic frameworks(COFs)is established based on rapid microwave-assisted anion exchange reaction and utilized to prepare a set of new COFs.Due to the interaction between the carbon dioxide(C02)and the acetate anion,the resulting SJTU-COF-AcO shows greatly enhanced carbon dioxide capacity up to 1.7 times of the pristine COF.The effect of the counteranions to CO2 capacity in the cationic COFs is investigated for the first time,which demonstrates that our channel-wall engineering strategy is a promising way to tailor the property of COFs for high CO2 capacity.     

Synthesis and self-assembly of dynamic covalent block copolymers: towards a general route to pore-functionalized membranes

A diblock copolymer is designed to have incompatible blocks, unsymmetrical block lengths, and a reversible linkage. This copolymer self-assembles into nanostructured cylindrical morphology in thin films. Removal of the nanosized cylinders by breaking the reversible linkage then affords nanoporous membranes featuring a chemically reactive functionality in the pores.     

Oil-water interfacial self-assembly: a novel strategy for nanofilm and nanodevice fabrication

How to integrate individual nanostructures into macroscopic thin films has become one of the most intriguing fields in nanoscience and nanotechnology due to the unique properties and important applications of these functional films. Since being discovered in 2004, oil-water interfacial self-assembly of nanostructures has become a novel strategy for fabrication of nanofilms. It is a powerful bottom-up approach for film fabrication due to the low cost and high efficiency, and is simple and universal for almost all low-dimensional nanostructures. In this article, we provide a critical review of the state-of-the-art research activities in this burgeoning self-assembly strategy. We first discuss the thermodynamic mechanism of the oil-water interfacial self-assembly, then the self-assembly of various low-dimensional nanostructures including nanoparticles, one-dimensional (1D) nanostructures, two-dimensional (2D) nanostructures at an oil-water interface developed so far to fabricate high-quality nanofilms. Finally, we present some progress on the construction of functional nanofilm-based nanodevices from this novel strategy based on our research. We conclude this review with critical comments on advantages and the experimental challenges, and further propose the future research and development of this self-assembly strategy for nanodevice construction (105 references).     

Hydrogen bonded aromatic hydrazide foldamers for the self-assembly of vesicles and gels

This paper describes an investigation of the structural and side-chain factors for the formation of vesicles and gels by hydrogen bonding-mediated aromatic hydrazide foldamers. Six foldamers and one straight analog that bear discrete side chains have been synthesized. SEM and AFM studies reveal that the molecules with the appended 2-(2-(dialkyl-amino)-2-oxoethylamino)-2-oxoethoxyl chains form vesicles, hydrogels or organogels, depending on the solvents. Both the inner amide units and the terminal N,N-dialkylamide units in the chains are revealed to play essential roles in controlling the self-assembly. The former facilitates it by forming the intermolecular hydrogen bonding, while the latter modulates it by providing solubility and balancing the hydrophobicity of the whole molecules in solvents of varying polarity.     

Non-enzymatic covalent protein labeling using a reactive tag

We describe herein a new method for covalent labeling of proteins using a complementary recognition pair of peptide tag and synthetic molecular probe. The rapid and specific covalent labeling of a tag-fused protein was achieved by the reaction on the tag site with the probe through their selective molecular recognition. The advantages of this method involve the facile functional modification and the high labeling specificity of the tag-fused protein, which are demonstrated in the labeling experiments in various conditions even inside cells.     

新型肼桥联共价三嗪聚合物在二氧化碳捕集和催化转化方面的应用（英文）

二氧化碳的捕集和催化转化是近年来二氧化碳利用方面的研究热点.其原因,一方面二氧化碳是储量丰富、廉价易得的可再生碳资源,另一方面它又是带来环境问题的温室气体.以金属有机框架、沸石和多孔聚合物材料为代表的同时具有规则孔道和活性催化位点的双功能材料为实践这一新概念创造了条件.但是,金属有机框架和沸石的应用面临由其自身结构所带来的热稳定性和/或水稳定性较低等问题.多孔聚合物材料则由于其高稳定性、低密度以及非金属等优点,逐渐成为该领域的研究重点.然而,当前关于利用多孔聚合物类材料作为有机催化剂以实现二氧化碳固定的报道,其反应过程一般需要较高温度、有机溶剂和/或过渡金属催化组分,仍有较大改进余地.本文设计合成了新型肼桥联共价三嗪聚合物(HB-CTP),意图在利用其富氮三嗪结构单元促进二氧化碳捕集的同时,以大量肼官能团通过氢键作用活化环氧化物,进而将二氧化碳在无溶剂和非金属的温和条件下催化固定为环状碳酸酯.HB-CTP材料的合成方法简便易行,由2,4,6-三肼基-1,3,5-三嗪与三聚氯氰发生的亲核取代反应制得.采用多种表征手段分析了该类新材料的结构和形态:红外光谱表明三聚氯氰的C–Cl键在聚合过程中反应完全,其位于850 cm.1处的吸收信号彻底消失;固体核磁谱图仅在168.1 ppm处显示三嗪环的单峰信号,表明了该材料结构的完整性;X射线粉末衍射测试并未发现特征峰,表明HB-CTP呈无定形态;透射电镜和扫描电镜的观测结果则进一步证实了该材料的团聚形态;最后,热重分析显示HB-CTP具有良好的热稳定性,250 ℃以上才开始分解.然后,通过氮气吸附测定了HB-CTP比表面积(51.2 m~2/g)和总孔容(0.28 cm3/g),其吸附等温线呈Ⅱ型,表明材料结构以大孔为主,通过层间吸附.随后的二氧化碳吸附测试发现,HB-CTP在0°C、0.1 MPa条件下显示出较高的二氧化碳捕集容量(8.2 wt%),并且经过连续吸附脱附循环五次,仍能保持较好的二氧化碳捕集能力.在HB-CTP材料良好的二氧化碳捕集容量基础上,本文考察了其催化活性,发现带有多种取代基的环氧化物均能在无溶剂、非金属的温和条件下,以较高的收率被转化为环状碳酸酯类产物;并且底物结构中的卤素、羟基、炔基、烯丙基和苄基等官能团均未发生副反应,显示出良好的底物适用范围.此外,HB-CTP材料可通过简单的离心操作实现分离回收,且经连续使用五次,其催化活性也没有明显降低.综上所述,该类新型肼桥联共价三嗪聚合物不仅能够高效捕集二氧化碳,而且还可以将其在温和条件下催化转化为环状碳酸酯类产物,具有一定理论研究意义和实际应用价值     

Bioorthogonal chemistry: a covalent strategy for the study of biological systems

The development of genetically encoded, wavelength-tunable fluorescent proteins has provided a powerful imaging tool to the study of protein dynamics and functions in cellular and organismal biology. However, many biological functions are not directly encoded in the protein primary sequence, e.g., dynamic regulation afforded by protein posttranslational modifications such as phosphorylation. To meet this challenge, an emerging field of bioorthogonal chemistry has promised to offer a versatile strategy to selectively label a biomolecule of interest and track their dynamic regulations in its native habitat. This strategy has been successfully applied to the studies of all classes of biomolecules in living systems, including proteins, nucleic acids, carbohydrates, and lipids. Whereas the incorporation of a bioorthogonal reporter site-selectively into a biomolecule through either genetic or metabolic approaches has been well established, the development of bioorthogonal reactions that allow fast ligation of exogenous chemical probes with the bioorthogonal reporter in living systems remains in its early stage. Here, we review the recent development of bioorthogonal reactions and their applications in various biological systems, with a detailed discussion about our own work—the development of the tetrazole based, photoinducible 1,3-dipolar cycloaddition reaction.     

Bioorthogonal chemistry:a covalent strategy for the study of biological systems

The development of genetically encoded,wavelength-tunable fluorescent proteins has provided a powerful imaging tool to the study of protein dynamics and functions in cellular and organismal biology.However,many biological functions are not directly encoded in the protein primary sequence,e.g.,dynamic regulation afforded by protein posttranslational modifications such as phosphorylation.To meet this challenge,an emerging field of bioorthogonal chemistry has promised to offer a versatile strategy to selective...     

High capacity gas capture and selectivity properties of triazatruxene-based ultramicroporous hyper-crosslinked covalent polymer

Tuning the selective sorption features of microporous organic networks is of great importance for subsequent applications in gas uptake and hiding, while it is more attractive in terms of being both time and cost effective to realize these optimizations without using functional groups in the core and linker. “Knitting” is one of the easiest and most used method to obtain a broad scope of hyper-crosslinked polymers on a large scale from aromatic structures that do not contain functional groups for polymerization. By the use of Knitting method, a hypercrosslinked covalent ultramicroporous organic polymer was obtained via stepwise process from using triazatruxene (TAT) as core -a planar indole trimer- through anhydrous FeCl₃ catalyzed Friedel–Crafts alkylation using dimethoxybenzene as a linker. The resulting microporous polymer, namely TATHCCP was completely identified by analytical and spectral techniques after examined for gas properties (CO₂, CH₄, O₂, CO, and H₂) and selectivity (CO₂/N₂, CO₂/O₂, for CO₂/CO and CO₂/CH₄) up to 1 bar and increased temperatures (273 K, 296 K and 320 K). Although it has a relatively low (Brunauer–Emmett–Teller) BET specific surface area around 557 m²/g, it was seen to have a high CO₂ capture capacity approaching 10% wt. at 273 K. In accordance with (ideal adsorbed solution theory) IAST computations, it was revealed that interesting selectivity features hitting up to 60 for CO₂/N₂, 45 for CO₂/O₂, 35 for CO₂/CO, 13 for CO₂/CH₄ at lower temperatures revealed that the material has much better selectivity values than many HCP (hyper-crosslinked polymer) derivatives in the literature even from its most similar analog dimethoxymethane derivative TATHCP, which has a surface area of 950 m²/g.     

Exploring the self-assembly of glycopeptides using a diphenylalanine scaffold

Diphenylalanine, a key building block for organic nanotechnology, forms discrete, rigid and hollow nanotubes that are assembled spontaneously upon their dilution from organic phase into aqueous solution. Here we report the efficient preparation of several S-linked glycosylated diphenylalanine analogues bearing different monosaccharide, di-saccharide and sialic acid residues. The self-assembly studies revealed that these glycopeptides adopted various structures and glycosylation could be a tool to manipulate the self-assembly process. Moreover, the solubility of these analogues was found to be much greater than diphenylalanine, which could open new applications based on these nanostructures.     

Mixed-element capture agents: a simple strategy for the construction of synthetic,high-affinity protein capture ligands

Demonstration of a simple strategy to generate synthetic high-affinity protein capture agents of practical utility for protein-detecting microarrays. The model study highlights capture of the MBP-Mdm2 fusion protein on a solid support by a linear sequence of peptides that bind to the two individual polypeptide chains.     

Facile synthesis of microporous carbonaceous materials derived from a covalent triazine polymer for CO_2 capture

Highly porous nitrogen-doped carbon materials were synthesized by the carbonization of a low-cost porous covalent triazine polymer, PCTP-3, which had been synthesized by the AlCl_3 catalyzed FriedelCrafts reaction of readily available monomers. The nature of the bond and structure of the resulting materials were confirmed using various spectroscopic methods, and the effects of KOH activation on the textural properties of the porous carbon materials were also examined. The KOH-activated porous carbon(aPCTP-3c) materials possessed a high surface area of 2271 m~2 g~(-1) and large micro/total pore volumes of 0.87/0.95 cm~3 g~(-1), respectively, with narrower micropore size distributions than the porous carbon prepared without activation(PCTP-3c). The aPCTP-3c exhibited the best CO_2 uptakes of 284.5 and 162.3 mg g~(-1) and CH_4 uptakes of 39.6 and 25.9 mg g~(-1) at 273 and 298 K/1 bar, respectively, which are comparable to the performance of some benchmark carbon materials under the same conditions. The prepared materials exhibited high CO_2/N_2 selectivity and could be regenerated easily.     

Lipase-catalyzed kinetic resolution on solid-phase via a "capture and release" strategy

The lipase-catalyzed kinetic resolution of (R/S)-3-phenylbutyric acid 2 using solid-supported cyclohexane-1,3-dione (CHD) 6 is described. In each case the predominant enantiomer observed, after cleavage from the resin, was (R)-(-)-3-phenylbutyric acid (R)-2 (ee > 99%) rather than the expected (S)-enantiomer of 2. This observation is in contrast to the fact that Chromobacterium viscosum lipase shows high enantiospecificity for the (S)-enantiomer in the corresponding solution-phase hydrolysis reactions. The (R)-acyl group was subsequently released from the resin by NaOH hydrolysis, and the yield of the reaction could be improved by triple acylation of the resin.     

A strategy for fabricating single layer graphene sheets based on a layer-by-layer self-assembly

A novel approach to synthesize graphene nanosheet is explored on the basis of the layer-by-layer (LbL) self-assembly of polyallylamine (PAA) and poly(styrene-sulfonate) (PSS) multi-layer with a metallic dopant.     

Synthesis of histone H3 proteins by a thioacid capture ligation strategy

The first application of thioacid capture ligation in protein synthesis is described. Two histone H3 proteins were synthesized in which a 30 min ligation reaction gave the protein products in good yields.