自组装合成超分子液晶聚合物研究进展

从电荷转移作用、离子相互作用、氢键作用组装、金属配位组装、光化学组装5个方面综述了通过分子自组装合成超分子液晶聚合物的近年来的最新研究成果,并介绍了超分子液晶聚合物的应用及发展前景。     

Predictive Engineering of Class I Terpene Synthases Using Experimental and Computational Approaches

Terpenoids are a highly diverse group of natural products with considerable industrial interest. Increasingly, engineered microbes are used for the production of terpenoids to replace natural extracts and chemical synthesis. Terpene synthases (TSs) show a high level of functional plasticity and are responsible for the vast structural diversity observed in natural terpenoids. Their relatively inert active sites guide intrinsically reactive linear carbocation intermediates along one of many cyclisation paths via exertion of subtle steric and electrostatic control. Due to the absence of a strong protein interaction with these intermediates, there is a remarkable lack of sequence-function relationship within the TS family, making product-outcome predictions from sequences alone challenging. This, in combination with the fact that many TSs produce multiple products from a single substrate hampers the design and use of TSs in the biomanufacturing of terpenoids. This review highlights recent advances in genome mining, computational modelling, high-throughput screening, and machine-learning that will allow more predictive engineering of these fascinating enzymes in the near future.     

Computational Evolution of Beta-2-Microglobulin Binding Peptides for Nanopatterned Surface Sensors

The bottom-up design of smart nanodevices largely depends on the accuracy by which each of the inherent nanometric components can be functionally designed with predictive methods. Here, we present a rationally designed, self-assembled nanochip capable of capturing a target protein by means of pre-selected binding sites. The sensing elements comprise computationally evolved peptides, designed to target an arbitrarily selected binding site on the surface of beta-2-Microglobulin (β2m), a globular protein that lacks well-defined pockets. The nanopatterned surface was generated by an atomic force microscopy (AFM)-based, tip force-driven nanolithography technique termed nanografting to construct laterally confined self-assembled nanopatches of single stranded (ss)DNA. These were subsequently associated with an ssDNA–peptide conjugate by means of DNA-directed immobilization, therefore allowing control of the peptide’s spatial orientation. We characterized the sensitivity of such peptide-containing systems against β2m in solution by means of AFM-based differential topographic imaging and surface plasmon resonance (SPR) spectroscopy. Our results show that the confined peptides are capable of specifically capturing β2m from the surface–liquid interface with micromolar affinity, hence providing a viable proof-of-concept for our approach to peptide design.     

Enhancing the Nucleolytic Resistance and Bioactivity of Functional Nucleic Acids by Diverse Nanostructures through in Situ Polymerization-Induced Self-assembly

Functional nucleic acids (FNAs) are garnering tremendous interest owing to their high modularity and unique bioactivity. Three-dimensional FNAs have been developed to overcome the issues of nuclease degradation and limited cell uptake. We have developed a new facile approach to the synthesis of multiple three-dimensional FNA nanostructures by harnessing photo-polymerization-induced self-assembly. Sgc8 aptamer and CpG oligonucleotide were modified as macro chain-transfer reagents to mediate in situ polymerization and self-assembly. Diverse structures, including micelles, rods, and short worms, afford these two FNAs afford these two FNAs with higher nuclease resistance in serum serum, greater cellular uptake efficiency, and increased bioactivity.     

计算化学在生物质气化研究中的应用

从可再生的生物质得到的替代能源是解决石油资源枯竭的方法之一。但生物质能的制备过程复杂,包括热解和反应速率较慢的气化过程。为了研究其反应机理,必须从实验和理论两方面入手。本综述介绍了生物质气化过程研究中应用的计算理论,并讨论了理论模型的类型、大小及电子结构的影响。此外,还对气化过程中的吸附、重排、迁移和解吸进行了综述。     

金属-有机骨架材料的计算化学研究

金属-有机骨架材料（metal-organic frameworks,MOFs）是一种新型纳米多孔材料,独特的结构特征使其在储气、分离、催化、生物化学及制药等领域具有广阔的潜在应用价值。本文综述了计算化学方法在探索MOF材料结构-性能关系方面的研究进展,并着重介绍了本研究室在此方面的研究成果。     

Computational Analysis of Molnupiravir

In this work, we report in-depth computational studies of three plausible tautomeric forms, generated through the migration of two acidic protons of the N⁴-hydroxylcytosine fragment, of molnupiravir, which is emerging as an efficient drug to treat COVID-19. The DFT calculations were performed to verify the structure of these tautomers, as well as their electronic and optical properties. Molecular docking was applied to examine the influence of the structures of the keto-oxime, keto-hydroxylamine and hydroxyl-oxime tautomers on a series of the SARS-CoV-2 proteins. These tautomers exhibited the best affinity behavior (−9.90, −7.90, and −9.30 kcal/mol, respectively) towards RdRp-RTR and Nonstructural protein 3 (nsp3_range 207–379-MES).     

Supramolecular Nanofibers of Peptide Amphiphiles for Medicine

Peptide nanostructures are an exciting class of supramolecular systems that can be designed for novel therapies with great potential in advanced medicine. This paper reviews progress on nanostructures based on peptide amphiphiles capable of forming one-dimensional assemblies that emulate in structure the nanofibers present in extracellular matrices. These systems are highly tunable using supramolecular chemistry, and can be designed to signal cells directly with bioactive peptides. Peptide amphiphile nanofibers can also be used to multiplex functions through co-assembly and designed to deliver proteins, nucleic acids, drugs, or cells. We illustrate here the functionality of these systems, describing their use in regenerative medicine of bone, cartilage, the nervous system, the cardiovascular system, and other tissues. In addition, we highlight recent work on the use of peptide amphiphile assemblies to create hierarchical biomimetic structures with order beyond the nanoscale, and also discuss the future prospects of these supramolecular systems.     

A Computational Framework for Magnetic Polyoxometalates and Molecular Spin Structures: CONDON 2.0

The emergence of increasingly complex molecular magnets, driven in particular by polyoxometalate chemistry, requires theoretical tools to accurately model and understand their magnetic phenomena. At the same time the unambiguous verification of model Hamiltonians remains a challenge, tied to factors ranging from available independent experimental data sets to available computation resources. Focusing on several recent examples for magnetically functionalized polyoxometalates and polynuclear coordination complexes, we demonstrate the recent developments of CONDON 2.0 that aim to address these issues, and suggest measurement protocols that will aid our multi-parameter computational approach.     

Mannose‐Decorated Multicomponent Supramolecular Polymers Trigger Effective Uptake into Antigen‐Presenting Cells

A modular route to prepare functional self‐assembling dendritic peptide amphiphiles decorated with mannosides, to effectively target antigen‐presenting cells, such as macrophages, is reported. The monomeric building blocks were equipped with tetra(ethylene glycol)s (TEGs) or labeled with a Cy3 fluorescent probe. Experiments on the uptake of the multifunctional supramolecular particles into murine macrophages (Mφs) were monitored by confocal microscopy and fluorescence‐activated cell sorting. Mannose‐decorated supramolecular polymers trigger a significantly higher cellular uptake and distribution, relative to TEG carrying bare polymers. No cytotoxicity or negative impact on cytokine production of the treated Mφs was observed, which emphasized their biocompatibility. The modular nature of the multicomponent supramolecular polymer coassembly protocol is a promising platform to develop fully synthetic multifunctional vaccines, for example, in cancer immunotherapy.     

Self-Assembling Peptide-Based Functional Biomaterials

Peptides can self-assemble into various hierarchical nanostructures through noncovalent interactions and form functional materials exhibiting excellent chemical and physical properties, which have broad applications in bio-/nanotechnology. The self-assembly mechanism, self-assembly morphology of peptide supramolecular architecture and their various applications, have been widely explored which have the merit of biocompatibility, easy preparation, and controllable functionality. Herein, we introduce the latest research progress of self-assembling peptide-based nanomaterials and review their applications in biomedicine and optoelectronics, including tissue engineering, anticancer therapy, biomimetic catalysis, energy harvesting. We believe that this review will inspire the rational design and development of novel peptide-based functional bio-inspired materials in the future.     

Approaches to Introduce Helical Structure in Cysteine-Containing Peptides with a Bimane Group

An i−i+4 or i−i+3 bimane-containing linker was introduced into a peptide known to target Estrogen Receptor alpha (ERα), in order to stabilise an α-helical geometry. These macrocycles were studied by CD and NMR to reveal the i−i+4 constrained peptide adopts a 3₁₀-helical structure in solution, and an α-helical conformation on interaction with the ERα coactivator recruitment surface in silico. An acyclic bimane-modified peptide is also helical, when it includes a tryptophan or tyrosine residue; but is significantly less helical with a phenylalanine or alanine residue, which indicates such a bimane modification influences peptide structure in a sequence dependent manner. The fluorescence intensity of the bimane appears influenced by peptide conformation, where helical peptides displayed a fluorescence increase when TFE was added to phosphate buffer, compared to a decrease for less helical peptides. This study presents the bimane as a useful modification to influence peptide structure as an acyclic peptide modification, or as a side-chain constraint to give a macrocycle.     

Solvent-Induced Self-Assembly of Highly Hydrophobic Tetra- and Pentaphenylalanine Peptides

Diphenylalanine peptide (FF) self-assembles into ordered structures of notable physical properties. Moreover, the ability of the phenylalanine amino acid or triphenylalanine to assemble into ordered nanostructures had been demonstrated. Herein, we explored the association potential of larger phenylalanine peptides, tetraphenylalanine, and pentaphenylalanine. A major challenge in studying the assembly of these peptides is their lack of solubility in different solvents. Yet, the remarkable capacity of acetic acid to solubilize FF was recently shown. Inspired by this, we examined whether this solvent could also be employed to dissolve these insoluble peptides. By utilizing the solvent-switch methodology, we revealed the self-assembly of tetraphenylalanine and pentaphenylalanine. The peptides were assembled into ordered autofluorescent elongated structures, which were further characterized by electron microscopy and spectroscopy analysis and could be utilized in future technological applications.     

Strategies for Stabilizing DNA Nanostructures to Biological Conditions

DNA is one of the most promising building blocks for creating functional nanostructures for applications in biology and medicine. However, these highly programmable nanomaterials (e.g., DNA origami) often require supraphysiological salt concentrations for stability, are degraded by nuclease enzymes, and can elicit an inflammatory response. Herein, three key strategies for stabilizing DNA nanostructures to conditions required for biological applications are outlined: 1) tuning the buffer conditions or nanostructure design; 2) covalently crosslinking the strands that make up the structures; and 3) coating the structures with polymers, proteins, or lipid bilayers. Taken together, these approaches greatly expand the chemical diversity and future applicability of DNA nanotechnology both in vitro and in vivo.     

Self-assembly in the ferritin nano-cage protein superfamily

Protein self-assembly, through specific, high affinity, and geometrically constraining protein-protein interactions, can control and lead to complex cellular nano-structures. Establishing an understanding of the underlying principles that govern protein self-assembly is not only essential to appreciate the fundamental biological functions of these structures, but could also provide a basis for their enhancement for nano-material applications. The ferritins are a superfamily of well studied proteins that self-assemble into hollow cage-like structures which are ubiquitously found in both prokaryotes and eukaryotes. Structural studies have revealed that many members of the ferritin family can self-assemble into nano-cages of two types. Maxi-ferritins form hollow spheres with octahedral symmetry composed of twenty-four monomers. Mini-ferritins, on the other hand, are tetrahedrally symmetric, hollow assemblies composed of twelve monomers. This review will focus on the structure of members of the ferritin superfamily, the mechanism of ferritin self-assembly and the structure-function relations of these proteins.     

Towards Supramolecular Catalysis with Small Self-assembled Peptides

Self-assembly of small peptides offers unique opportunities for the bottom-up construction of supramolecular catalysts that aim to emulate the efficiency and selectivity of natural enzymes. Small, information-rich, simple molecules based on amino acids can self-organise autonomously into complex systems with emergent catalytic properties. The power of noncovalent interactions can be used to construct supramolecular peptidic tertiary structures. Moreover, specific functional groups present in amino acid side-chains may present either a catalytic activity by themselves or be able to bind cofactors such as metal ions. In this scenario, although relevant progress has been achieved in recent years, promising applications in biomaterials science are foreseen. In this review, we discuss the state-of-the-art of this approach at the interface between supramolecular chemistry and peptide science.     

Computational Chemistry in the Pharmaceutical Industry: From Childhood to Adolescence

Computational chemistry within the pharmaceutical industry has grown into a field that proactively contributes to many aspects of drug design, including target selection and lead identification and optimization. While methodological advancements have been key to this development, organizational developments have been crucial to our success as well. In particular, the interaction between computational and medicinal chemistry and the integration of computational chemistry into the entire drug discovery process have been invaluable. Over the past ten years we have shaped and developed a highly efficient computational chemistry group for small‐molecule drug discovery at Bayer HealthCare that has significantly impacted the clinical development pipeline. In this article we describe the setup and tasks of the computational group and discuss external collaborations. We explain what we have found to be the most valuable and productive methods and discuss future directions for computational chemistry method development. We share this information with the hope of igniting interesting discussions around this topic.     

两亲性淀粉自组装研究进展

两亲性淀粉具有独特的结构特征,将其溶于选择性溶剂中,在疏水力的推动下会自组装形成核-壳结构的球形胶束.胶束可包合疏水性客体,对客体进行空间束缚,形成超分子包合物.两亲性淀粉自组装扩大了淀粉作为载体的应用范围.总结了两亲性淀粉自组装的原理、制备方法、影响因素,介绍了该方法应用于食品、医药、工业领域的研究进展,并提出了目前...