Solution Conformation Research Articles

Pairing instabilities of the Yukawa-SYK models with controlled fermion incoherence

The interplay of non-Fermi liquid and superconductivity born out of strong dynamical interactions is at the heart of the physics of unconventional superconductivity. As a solvable platform of the strongly correlated superconductors, we study the pairing instabilities of the Yukawa-Sachdev-Ye-Kitaev (Yukawa-SYK) model, which describes spin-1/2 fermions coupled to bosons by the random, all-to-all, spin-independent and dependent Yukawa interactions. In contrast to the previously studied models, the random Yukawa couplings are sampled from a collection of Gaussian ensembles whose variances follow a continuous distribution rather than being fixed to a constant. By tuning the analytic behaviour of the distribution, we could control the fermion incoherence to systematically examine various normal states ranging from the Fermi liquid to non-Fermi liquids that are different from the conformal solution of the SYK model with a constant variance. Using the linearised Eliashberg theory, we show that the onset of the unconventional spin-triplet pairing is preferred with the spin-dependent interactions while all pairing channels show instabilities with the spin-independent interactions. Although the interactions shorten the lifetime of the fermions in the non-Fermi liquid, the same interactions also dress the bosons to strengthen the tendency to pair the incoherent fermions. As a consequence, the onset temperature T_cTc of the pairing is enhanced in the non-Fermi liquid compared to the case of the Fermi liquid.

Molecular Basis for Regulation of Mammalian Fatty Acid Synthase

De novo lipogenesis (DNL) is an essential metabolic process that converts excess cellular glucose to fatty acids. Fatty Acid Synthase (FASN) is a key enzyme in the DNL pathway and has shown promising pre‐clinical results as a therapeutic target in a variety of metabolic diseases, including cancer, non‐alcoholic fatty liver disease (NAFLD), and most recently COVID‐19. Mammalian FASN is a large multifunctional enzyme with 6 catalytic domains and a flexibly tethered acyl carrier protein (ACP). The ACP shuttles covalently linked intermediates between catalytic domains to facilitate palmitate synthesis. Previous negative stain electron microscopy data has shown that mammalian FASN is a dynamic enzyme that adopts multiple conformations in solution, but the role of these conformational dynamics in the mechanism of FASN is yet to be determined. To understand how the conformational dynamics of mammalian FASN contribute to the overall mechanism and its’ regulation, we have generated multiple constructs and characterized their enzymatic activity using diverse biochemical assays. Additionally, we have made progress towards understanding the enzyme dynamics using Hydrogen‐Deuterium Exchange Mass Spectrometry (HDX‐MS). We are actively pursuing structural studies to implement an integrative approach towards advancing our understanding of the complex mechanism of mammalian FASN.

Electrochemical evaluation of the grafting density of self-assembled monolayers of polyethylene glycol of different chain lengths formed by the grafting to approach under conditions close to the cloud point

• The grafting density of the SAMs of polymer films is a useful parameter that is very difficult to obtain. • SAMs of polyethylene glycol built from good solvents like water, maintain their solution conformation upon adsorption. • The presence of high amount of water in the polyethylene glycol SAMs is responsible of the high charge density obtained in the reductive desorption process. • The SAMs of polyethylene glycol formed under cloud point conditions exclude most of the water giving more realistic grafting density values. • The proposed methodology to get grafting densities of polyethylene glycol SAMs can be easily extended to other polymer SAMs. Grafting densities of polymers on gold surfaces are important parameters that inform about the chain conformation adopted by the chains, either mushroom or brush conformation. Most of the literature reports on this topic are based on ellipsometry measurements with other few results obtained from surface plasmon resonance or quartz crystal microbalance. In this work, we report the use of cyclic voltammetry of the reductive desorption (RD) process of mercapto-polyethylene glycol self-assembled monolayers (EGn-SAMs) to get the grafting densities of these polymers with different chain lengths (c.a. EG136, EG45 and EG18). When the EGn-SAMs are formed from aqueous solutions where the polymer chains are highly hydrated, an excess of charge density is obtained that apart from the capacitive contribution found in these processes, include an extra charge due to the hydrogen evolution reaction (HER) produced by the high ratio of water contained in the film that reduces concomitantly with the SAM RD process. However, preparing the EGn-SAM in the presence of high salt concentrations that lowers the water content within the chains, that is, using the cloud point strategy, very realistic grafting density values are obtained. The RD profiles of the EGn-SAMs completely change from a broad peak with high charge density to a structured peak that allows us the determination of grafting density values. Capacitance curves and the behavior of the electrochemical process of the Fe(CN) 6 3-/4- redox pair in the presence of the films are also in agreement with the CV results. The grafting density values obtained by this methodology are higher than those reported for these SAMs by using other techniques but agree with the footprints expected for these chains when organized in a brush conformation. Moreover, they also are close to the values obtained by thermogravimetric analysis of the same films built on gold nanoparticles that behave as planar surfaces.

Molecular dynamics simulation of α‐gliadin in ethanol/aqueous organic solvents

SummaryGliadin is an important protein present in cereals. Owing to its solubility in alcohol, gliadin contributes significantly to the field of food industry. However, at present, it is challenging to study the structural characteristics of gliadin at the molecular level because the exact 3‐D structure cannot be obtained using experimental methods. In this study, an α‐gliadin model was constructed by combining homology modelling, ab initio modelling, and threading methods to study the structural properties of gliadin in ethanol aqueous solution. Our results indicated that glutamine is a key element of α‐gliadin. Also, α‐gliadin exhibited relatively low hydrophilicity and high lipid solubility. Molecular dynamics simulations suggested that there are hydrogen bonds and van der Waals forces existed between α‐gliadin and ethanol molecules. This study has explored the structure of wheat gliadin and its conformation in different ethanol solutions and provides a deeper understanding towards the deacetylation mechanism and potential applications of α‐gliadin in the food industry.

Structural Characterization of the Full-Length Anti-CD20 Antibody Rituximab.

Rituximab, a murine–human chimera, is the first monoclonal antibody (mAb) developed as a therapeutic agent to target CD20 protein. Its Fab domain and its interaction with CD20 have been extensively studied and high-resolution atomic models obtained by X-ray diffraction or cryo-electron microscopy are available. However, the structure of the full-length antibody is still missing as the inherent protein flexibility hampers the formation of well-diffracting crystals and the reconstruction of 3D microscope images. The global structure of rituximab from its dilute solution is here elucidated by small-angle X-ray scattering (SAXS). The limited data resolution achievable by this technique has been compensated by intensive computational modelling that led to develop a new and effective procedure to characterize the average mAb conformation as well as that of the single domains. SAXS data indicated that rituximab adopts an asymmetric average conformation in solution, with a radius of gyration and a maximum linear dimension of 52 Å and 197 Å, respectively. The asymmetry is mainly due to an uneven arrangement of the two Fab units with respect to the central stem (the Fc domain) and reflects in a different conformation of the individual units. As a result, the Fab elbow angle, which is a crucial determinant for antigen recognition and binding, was found to be larger (169°) in the more distant Fab unit than that in the less distant one (143°). The whole flexibility of the antibody has been found to strongly depend on the relative inter-domain orientations, with one of the Fab arms playing a major role. The average structure and the amount of flexibility has been studied in the presence of different buffers and additives, and monitored at increasing temperature, up to the complete unfolding of the antibody. Overall, the structural characterization of rituximab can help in designing next-generation anti-CD20 antibodies and finding more efficient routes for rituximab production at industrial level.

Synthesis and characterization of block copolymers of styrene‐maleic acid with acrylamide and N,N‐dimethylacrylamide

AbstractStyrene‐maleic acid (SMA) block copolymers with either acrylamide (AM) or N,N‐dimethylacrylamide (DMA) have been synthesized via a 3‐step process comprising: (1) photopolymerization of styrene and maleic anhydride in solution to yield an alternating styrene maleic anhydride (SMAnh) copolymer, (2) copolymerization of SMAnh with either AM or DMA to yield SMAnh‐b‐AM and SMAnh‐b‐DMA block copolymers and (3) hydrolysis of the anhydride groups to yield water‐soluble SMA‐b‐AM and SMA‐b‐DMA block copolymers as the final products. With a view to their intended application in membrane protein solubilization, molecular weights are controlled to below 10,000 by the synthesis conditions employed in step (1), including using carbon tetrabromide (CBr4) as a chain transfer agent. The CBr4 also plays an important role in step (2). By terminating the SMAnh chain radicals from step (1) with C‐Br bonds that are photolytically active, SMAnh chain radicals can be regenerated to act as macroinitiators for the polymerization of AM or DMA in step (2). Finally, following step (3) and due to the pH‐dependency of the SMA chain conformation in solution, a pH of 7–8 is found to be optimal for enabling the final products to be precipitated in a solid form that is completely soluble in water.

Identification of the Principle of Taste Sensors to Detect Non-Charged Bitter Substances by 1H-NMR Measurement.

A taste sensor with lipid/polymer membranes is attracting attention as a method to evaluate taste objectively. However, due to the characteristic of detecting taste by changes in membrane potential, taste sensors cannot measure non-charged bitter substances. Many foods and medicines contain non-charged bitter substances, and it is necessary to quantify these tastes with sensors. Therefore, we have been developing taste sensors to detect bitter tastes caused by non-charged substances such as caffeine. In previous studies, a sensor for detecting bitterness caused by caffeine and theobromine, theophylline, was developed, using a membrane modified with hydroxybenzoic acid (HBA) as the sensing part. The sensor was designed to form intramolecular hydrogen bonds (H-bonds) between the hydroxy group and carboxy group of HBA and to successively cause the intermolecular H-bonds between HBA and caffeine molecules to be measured. However, whether this sensing principle is correct or not cannot be confirmed from the results of taste sensor measurements. Therefore, in this study, we explored the interaction between HBA and caffeine by 1H-nuclear magnetic resonance spectroscopy (NMR). By the 1H NMR detection, we confirmed that both the substances interact with each other. Furthermore, the nuclear Overhauser effect (NOE) of intermolecular spatial conformation in solution was measured, by which 2,6-dihydroxybenzoic acid (2,6-DHBA) preferably interacted with caffeine via the H-bonding and stacking configuration between aromatic rings. Identifying the binding form of 2,6-DHBA to caffeine was estimated to predict how the two substances interact.

Supramolecular structure features and immunomodulatory effects of exopolysaccharide from Paecilomyces cicadae TJJ1213 in RAW264.7 cells through NF-κB/MAPK signaling pathways

This study investigated the supramolecular structure features and immunomodulatory effects of two exopolysaccharide fractions (EPS1 and EPS2) from Paecilomyces cicada TJJ1213 in vitro. AFM images revealed that EPS1 and EPS2 displayed different morphological features at different concentrations. Congo red and XRD assay further proved that EPS1 and EPS2 mainly exhibited amorphous structure with random coil conformation in solution. Furthermore, the immunomodulatory effect of EPSs was investigated on RAW264.7 cells. Results showed that EPS1 and EPS2 could enhance the phagocytic activity and induce the NO production and could also significantly up-regulate the mRNA expression of iNOS, TNF-α, IL-6, IL-1β, IFN-γ and IL-4. Western blot assay analysis demonstrated that EPSs increased protein expression of TLR4 and the nuclear translocation of NF-κB p50/p65. Additionally, the phosphorylation levels of MAPKs proteins (p38, ERK and JNK) were also remarkably increased. Thus, EPSs could active TLR4-NF-κB/MAPKs signaling pathways to exert the immunomodulatory effect on macrophages.

Conformational Transitions in Yeast Chorismate Mutase Important for Allosteric Regulation as Identified by Nuclear Magnetic Resonance Spectroscopy

Proteins fluctuate between different conformations in solution, and these conformational fluctuations can be important for protein function and allosteric regulation. The chorismate mutase from Saccharomyces cerevisiae (ScCM), a key enzyme in the biosynthesis of aromatic amino acids, is allosterically activated and inhibited by tryptophan and tyrosine, respectively. It was initially proposed that in the absence of effector, ScCM fluctuates between activated R and inhibited T conformations according to the Monod-Wyman-Changeux (MWC) model, although a more complex regulation pattern was later suggested by mutagenesis and kinetic data. Here we used NMR relaxation dispersion experiments to understand the conformational fluctuations on the microsecond-to-millisecond timescale that occur in ScCM. In the absence of allosteric effectors, ScCM did not exclusively exchange between T and R conformations, suggesting that the two-state MWC model is insufficient to explain conformational dynamics. Addition of tyrosine led to the quenching of much of the motion on this timescale, while new motions were identified in the presence of tryptophan. These new motions are consistent with conformational fluctuations into an alternative conformation that may be important for enzyme activity.

Cove‐Edged Hexa‐peri‐hexabenzo‐bis‐peri‐octacene: Molecular Conformations and Amplified Spontaneous Emission

AbstractThe bottom‐up synthesis of an unprecedentedly large cove‐edged nanographene, hexa‐peri‐hexabenzo‐bis‐peri‐octacene (HBPO), is reported in this work. Chiral high‐performance liquid chromatography and density functional theory (DFT) calculations revealed multiple conformations in solution. Two different molecular conformations, “waggling” and “butterfly”, were found in crystals by X‐ray crystallography, and the selectivity of conformations could be tuned by solvents. The optoelectronic properties of HBPO were investigated by UV/Vis absorption and fluorescence spectroscopies, cyclic voltammetry, and DFT calculations. The contorted geometry and branched alkyl groups suppress the aggregation of HBPO in solution, leading to a high fluorescence quantum yield of 79 %. The optical‐gain properties were explored through transient absorption and amplified spontaneous emission spectroscopies, which enrich the choices of edge structures for potential applications in laser cavities.

Cove-Edged Hexa-peri-hexabenzo-bis-peri-octacene: Molecular Conformations and Amplified Spontaneous Emission.

The bottom‐up synthesis of an unprecedentedly large cove‐edged nanographene, hexa‐peri‐hexabenzo‐bis‐peri‐octacene (HBPO), is reported in this work. Chiral high‐performance liquid chromatography and density functional theory (DFT) calculations revealed multiple conformations in solution. Two different molecular conformations, “waggling” and “butterfly”, were found in crystals by X‐ray crystallography, and the selectivity of conformations could be tuned by solvents. The optoelectronic properties of HBPO were investigated by UV/Vis absorption and fluorescence spectroscopies, cyclic voltammetry, and DFT calculations. The contorted geometry and branched alkyl groups suppress the aggregation of HBPO in solution, leading to a high fluorescence quantum yield of 79 %. The optical‐gain properties were explored through transient absorption and amplified spontaneous emission spectroscopies, which enrich the choices of edge structures for potential applications in laser cavities.

Human CEACAM1 N-domain dimerization is independent from glycan modifications

Carcinoembryonic cellular adhesion molecules (CEACAMs) serve diverse roles in cell signaling, proliferation, and survival and are made up of one or several immunoglobulin (Ig)-like ectodomains glycosylated invivo. The physiological oligomeric state and how it contributes to protein function are central to understanding CEACAMs. Two putative dimer conformations involving different CEACAM1 N-terminal Ig-like domain (CCM1) protein faces (ABED and GFCC'C″) were identified from crystal structures. GFCC'C″ was identified as the dominant CCM1 solution dimer, but ambiguity regarding the effect of glycosylation on dimer formation calls its physiological relevance into question. We present the first crystal structure of minimally glycosylated CCM1 in the GFCC'C″ dimer conformation and characterization in solution by continuous-wave and double electron-electron resonance electron paramagnetic resonance spectroscopy. Our results suggest the GFCC'C″ dimer is dominant in solution with different levels of glycosylation, and structural conservation and co-evolved residues support that the GFCC'C″ dimer is conserved across CEACAMs.

The suppressor of copper sensitivity protein C from Caulobacter crescentus is a trimeric disulfide isomerase that binds copper(I) with subpicomolar affinity.

The introduction of disulfide bonds into periplasmic proteins is a critical process in many Gram-negative bacteria. The formation and regulation of protein disulfide bonds have been linked to the production of virulence factors. Understanding the different pathways involved in this process is important in the development of strategies to disarm pathogenic bacteria. The well characterized disulfide bond-forming (DSB) proteins play a key role by introducing or isomerizing disulfide bonds between cysteines in substrate proteins. Curiously, the suppressor of copper sensitivity C proteins (ScsCs), which are part of the bacterial copper-resistance response, share structural and functional similarities with DSB oxidase and isomerase proteins, including the presence of a catalytic thioredoxin domain. However, the oxidoreductase activity of ScsC varies with its oligomerization state, which depends on a poorly conserved N-terminal domain. Here, the structure and function of Caulobacter crescentus ScsC (CcScsC) have been characterized. It is shown that CcScsC binds copper in the copper(I) form with subpicomolar affinity and that its isomerase activity is comparable to that of Escherichia coli DsbC, the prototypical dimeric bacterial isomerase. It is also reported that CcScsC functionally complements trimeric Proteus mirabilis ScsC (PmScsC) in vivo, enabling the swarming of P. mirabilis in the presence of copper. Using mass photometry and small-angle X-ray scattering (SAXS) the protein is demonstrated to be trimeric in solution, like PmScsC, and not dimeric like EcDsbC. The crystal structure of CcScsC was also determined at a resolution of 2.6 Å, confirming the trimeric state and indicating that the trimerization results from interactions between the N-terminal α-helical domains of three CcScsC protomers. The SAXS data analysis suggested that the protomers are dynamic, like those of PmScsC, and are able to sample different conformations in solution.

Protocol for characterizing the molar mass distribution and oxidized functionality profiles of aged transformer papers by gel permeation chromatography (GPC)

Oil-immersed paper insulation and paper pressboards for structural support are widely used in electrical power transformers. Cellulose thus fulfills an essential task for the smooth power supply of our societies. However, the prevailing temperatures in such equipment, combined with a targeted service life of several decades, pose a serious challenge to the long-term integrity of cellulosic paper insulation. Therefore, numerous studies have been conducted to obtain kinetic data on the degradation processes that contribute to the thermally induced decomposition of cellulose. These studies usually rely on the assessment of the average degree of polymerization by viscosity measurements. In this work, we applied and optimized more advanced methods for the characterization of cellulosic materials based on gel permeation chromatography for the special case of thermally stressed unbleached Kraft paper samples. This allowed studying the molar mass distributions of paper polymers upon exposure to heat, as well as the investigation of changes in their conformation in solution and the observation of thermally induced cross-linking. In combination with group-selective fluorescence labeling, it was possible to track over time the changes in molar mass-dependent profiles of carbonyl and carboxyl groups of authentic Kraft insulator paper samples under thermal stress. In addition, changes of the hemicellulose composition were quantified. We hope that this analytical approach to the in-depth characterization of thermally stressed insulator paper will prove useful for future studies of this important cellulose product, and that our findings will contribute to a better understanding of the thermal decomposition of paper in general.Graphical abstract

Purification and characterization of dextranase from Penicillium cyclopium CICC-4022 and its degradation of dextran

A dextranase was purified from Penicillium cyclopium CICC-4022 by ammonium sulfate fractionation and secondary tangential flow filtration, and the enzymatic properties were studied. The purified dextranase was used to regulated the molecular mass and homogeneity of dextran. Weight-average molecular mass (Mw) and polydispersity index (Mw/Mn) of dextran were measured by gel permeation chromatography (GPC) coupled with a triple-detector array (GPC-TDA), which is composed of a multiple-angle light scattering, a viscometer, and a refractive-index detector. The dextranase was purified by 2.24-fold, the recovery rate was 45.84%, the specific activity was 1442.05 U/mg, and the Mw was 77 KDa. Dextranase showed maximum activity at pH of 5.0 and 55 °C. Na+, K+ and NH4+ can effectively improve the dextranase activity, Cu2+ and Pb2+ can strongly inhibit the dextranase activity. Dextranase specifically degraded the α-1,6 glycosidic bonds of dextran. By controlling the dextranase activity, substrate concentration, and time, the specific Mw dextran with good homogeneity was obtained. The structure of dextran was not altered before or after dextranase hydrolysis, but its conformation changed from a spherical chain to a compliant chain. When the Mw of the dextran product was about 5 KDa, it was a compact spherical chain conformation in solution.

Assessment of prediction methods for protein structures determined by NMR in CASP14: impact of AlphaFold2

NMR studies can provide unique information about protein conformations in solution. In CASP14, three reference structures provided by solution NMR methods were available (T1027, T1029, and T1055), as well as a fourth data set of NMR-derived contacts for an integral membrane protein (T1088). For the three targets with NMR-based structures, the best prediction results ranged from very good (GDT_TS = 0.90, for T1055) to poor (GDT_TS = 0.47, for T1029). We explored the basis of these results by comparing all CASP14 prediction models against experimental NMR data.

Shaping Macromolecules for Sensing Applications-From Polymer Hydrogels to Foldamers.

Sensors are tools for detecting, recognizing, and recording signals from the surrounding environment. They provide measurable information on chemical or physical changes, and thus are widely used in diagnosis, environment monitoring, food quality checks, or process control. Polymers are versatile materials that find a broad range of applications in sensory devices for the biomedical sector and beyond. Sensory materials are expected to exhibit a measurable change of properties in the presence of an analyte or a stimulus, characterized by high sensitivity and selectivity of the signal. Signal parameters can be tuned by material features connected with the restriction of macromolecule shape by crosslinking or folding. Gels are crosslinked, three-dimensional networks that can form cavities of different sizes and forms, which can be adapted to trap particular analytes. A higher level of structural control can be achieved by foldamers, which are macromolecules that can attain well-defined conformation in solution. By increasing control over the three-dimensional structure, we can improve the selectivity of polymer materials, which is one of the crucial requirements for sensors. Here, we discuss various examples of polymer gels and foldamer-based sensor systems. We have classified and described applied polymer materials and used sensing techniques. Finally, we deliberated the necessity and potential of further exploration of the field towards the increased selectivity of sensory devices.

Research on Extraction, Structure Characterization and Immunostimulatory Activity of Cell Wall Polysaccharides from Sparassis latifolia.

The cell wall polysaccharides were extracted from Sparassis latifolia fruit bodies by acid–alkali and superfine-grinding assisted methods, and the chemical characterization and in vitro immunity activities of these polysaccharide fractions were studied and compared. Results showed that superfine-grinding assisted extraction exhibited the highest yield of polysaccharides (SP, 20.80%) and low β-glucan content (19.35%) compared with alkaline extracts. The results revealed that the 20% ethanol precipitated fraction (20E) from SP was mainly composed of β-(1→3)-glucan and α-(1→4)-glucan. With the increase of ethanol precipitation, the fractions (30E, 40E, 50E) were identified as α-(1→4)-glucan with different molecular weights and conformations. Cell wall polysaccharides extracted through NaOH (NSP) and KOH (KSP) extraction had similar yields with 8.90% and 8.83%, respectively. Structural analysis indicated that the purified fraction from KSP (KSP-30E) was a β-(1→3)-glucan backbone branched with β-(1→6)-Glcp, while the purified fraction from NSP (NSP-30E) mainly contained β-(1→3)-glucan with a small number of α-linked-Glcp. The two fractions both exhibited rigid chain conformation in aqueous solutions. All polysaccharide fractions exerted the activity of activating Dectin-1 receptor in vitro, and the KSP-30E mainly identified as β-(1→3)-glucan with the terminal group via 1→6-linkage attached at every third residue exhibited a stronger enhancing effect than other fractions. Results suggested that KOH extraction could be efficient for the preparation of bioactive β-(1→3, 1→6)-glucan as a food ingredient.

A Disulfide-Stabilized Aβ that Forms Dimers but Does Not Form Fibrils.

Aβ dimers are a basic building block of many larger Aβ oligomers and are among the most neurotoxic and pathologically relevant species in Alzheimer's disease. Homogeneous Aβ dimers are difficult to prepare, characterize, and study because Aβ forms heterogeneous mixtures of oligomers that vary in size and can rapidly aggregate into more stable fibrils. This paper introduces AβC18C33 as a disulfide-stabilized analogue of Aβ42 that forms stable homogeneous dimers in lipid environments but does not aggregate to form insoluble fibrils. The AβC18C33 peptide is readily expressed in Escherichia coli and purified by reverse-phase HPLC to give ca. 8 mg of pure peptide per liter of bacterial culture. SDS-PAGE establishes that AβC18C33 forms homogeneous dimers in the membrane-like environment of SDS and that conformational stabilization of the peptide with a disulfide bond prevents the formation of heterogeneous mixtures of oligomers. Mass spectrometric (MS) studies in the presence of dodecyl maltoside (DDM) further confirm the formation of stable noncovalent dimers. Circular dichroism (CD) spectroscopy establishes that AβC18C33 adopts a β-sheet conformation in detergent solutions and supports a model in which the intramolecular disulfide bond induces β-hairpin folding and dimer formation in lipid environments. Thioflavin T (ThT) fluorescence assays and transmission electron microscopy (TEM) studies indicate that AβC18C33 does not undergo fibril formation in aqueous buffer solutions and demonstrate that the intramolecular disulfide bond prevents fibril formation. The recently published NMR structure of an Aβ42 tetramer (PDB: 6RHY) provides a working model for the AβC18C33 dimer, in which two β-hairpins assemble through hydrogen bonding to form a four-stranded antiparallel β-sheet. It is anticipated that AβC18C33 will serve as a stable, nonfibrilizing, and noncovalent Aβ dimer model for amyloid and Alzheimer's disease research.

Deep eutectic solvents boosting solubilization and Se-functionalization of heteropolysaccharide: Multiple hydrogen bonds modulation

In this study, the favorable feasibility of deep eutectic solvents (DESs) in solubilization and functionalization of natural heteropolysaccharide was validated by experiments and density functional theory calculations. This revealed that choline chloride-based DES/DMSO (dimethyl sulfoxide) binary mixed solvents possessed more and stronger hydrogen bonding sites, facilitating the balance between disruption and reconstruction of hydrogen bonds within branched heteropolysaccharide from Artemisia sphaerocephala (PAS) and achieving efficient solubilization. Further, due to the full exposure and activation of polysaccharide hydroxyls, the efficiency of DES/DMSO-mediated novel Se-functionalization was substantially enhanced compared to the conventional selenylation methods. The derivative exhibited conversion to lower molecular mass with rigid solution conformation based on co-solvent effect and predominant acidic environment influence. This study offered a framework for exploring the potential of individualized polysaccharide functionalization by modulating DES constituents to achieve multiple controllabilities in terms of conversion efficiency and derivative structure.