Search Results (101)

Pharmacological chaperones of heterogeneous nuclear ribonucleoproteins (hnRNPs) show promise as potential neuroprotective drug candidates. They are expected to prevent the accumulation of neurotoxic hnRNP biocondensates and aggregates, which are hallmarks of severe degenerative diseases. Here, we present the first rational design of oligonucleotide chaperones of hnRNP A1. This design was inspired by previous studies on the specificity of the RNA recognition motif (RRM) and the RGG motif of hnRNP A1 for endogenous nucleic acids. To obtain robust and specific chaperones, we combined an RRM-binding sequence with an RGG-binding G-quadruplex oligonucleotide that inhibits hnRNP A1 aggregation and introduced various modifications into the sugar-phosphate backbone of the oligonucleotide. Modifications that locked the RRM-binding sequence in a conformational state characteristic of RNA improved chaperone affinity and activity. The former was assessed using microscale thermophoresis assays, while the latter was evaluated using fluorimetry and microscopy. The leading chaperone bound to hnRNP A1 at micromolar concentrations and inhibited the assembly of its condensates and amyloid-like aggregates (fibrils) by over 90%. Full article

Control strategies for leishmaniasis increasingly target sand fly vectors through sugar feeding approaches containing bioactive compounds. This study investigated the behavioral and toxicological effects of the iridoids plumericin and isoplumericin, isolated from Himatanthus sucuuba, on Lutzomyia longipalpis by integrating computational and experimental approaches focused on gustatory system interactions. The iridoids were purified by column chromatography and characterized by GC-MS. The gustatory receptor A0A1B0CHD5 was structurally characterized through homology modeling, followed by molecular docking and 100 ns molecular dynamics simulations. Behavioral assays evaluated survival, repellency, and feeding preferences using sugar solutions supplemented with an iridoid mixture. Toxicity was assessed in Drosophila melanogaster as a non-target organism model. Molecular docking results revealed comparable binding affinities between sucrose (ChemPLP score 57.96) and the iridoids plumericin (49.08) and isoplumericin (47.75). Molecular dynamics simulations confirmed the stability of the ligand–receptor complexes and revealed distinct conformational changes. The iridoids did not affect L. longipalpis survival, showed no repellency, and did not reduce sugar feeding acceptance. Preference for the control diet was observed only after continuous exposure (48 h), suggesting involvement of post-ingestive sensory processing. No acute toxicity was observed in D. melanogaster (96% survival). These findings demonstrate that iridoids preserve vector feeding behavior and survival while exhibiting low toxicity to non-target organisms, supporting their potential use in gustatory modulation strategies in leishmaniasis vector control without compromising ecological safety. Full article

Sugar amino acids (SAAs) represent a privileged class of molecular chimeras that uniquely merge the structural rigidity of carbohydrates with the functional display of amino acids. These hybrid molecules have garnered significant attention as programmable conformational constraints, offering a powerful strategy to overcome the inherent limitations of peptide-based therapeutics, such as proteolytic instability and conformational ambiguity. The strategic incorporation of SAAs into peptide backbones, particularly within cyclic frameworks, allows for the rational design of peptidomimetics with pre-organized secondary structures, enhanced metabolic stability, and improved physicochemical properties. This review provides a comprehensive analysis of the synthetic methodologies developed to access the diverse structural landscape of SAAs, with a focus on modern, stereoselective strategies that yield versatile building blocks for peptide chemistry. A critical examination of the structural impact of SAA incorporation reveals their profound ability to induce and stabilize specific secondary structures, such as β- and γ-turns. Furthermore, a comparative analysis positions SAAs in the context of other widely used peptidomimetic scaffolds, highlighting their unique advantages in combining conformational control with tunable hydrophilicity. We surveyed the application of SAA-containing cyclic peptides as therapeutic agents, with a detailed case study on gramicidin S analogs that underscores the power of SAAs in elucidating complex structure–activity relationships. Finally, this review presents a forward-looking perspective on the challenges and future directions of the field, emphasizing the transformative potential of computational design, artificial intelligence, and advanced bioconjugation techniques to accelerate the development of next-generation SAA-based therapeutics. Full article

I-motifs are non-canonical, cytosine-rich DNA structures stabilized by hemiprotonated C•C⁺ base pairs, whose formation is highly pH-dependent. While certain chemical modifications can enhance i-motif stability, modifications at the sugar moiety often disrupt essential inter-strand contacts. In this study, we examine the structural and thermodynamic impact of incorporating 2′-fluoro-ribocytidine (2′F-riboC) into i-motif-forming sequences derived from d(TCCCCC). Using a combination of UV, ¹H NMR, and ¹⁹F NMR spectroscopy, we demonstrate that full substitution with 2′F-riboC strongly destabilizes i-motif, whereas partial substitutions (one or two substitutions per strand) support well-folded structures at acidic pH (pH 5). High-resolution NMR structures reveal well-defined i-motif architectures with conserved C•C⁺ pairing and characteristic interstrand NOEs. Sugar conformational analysis reveals a predominant North pucker for cytosines, which directs the fluorine substituent toward the minor groove of the i-motif. ¹⁹F NMR further confirms slow exchange between folded and unfolded species, enabling the simultaneous detection of both under identical experimental conditions and, consequently, highlighting the utility of fluorine at the 2′ sugar position as a spectroscopic probe. These findings provide insights into fluorine-mediated modulation of i-motif stability and further extend the utility of ¹⁹F NMR in nucleic acid research. Full article

d-Tagatose, classified as a rare sugar, exhibits notable biological activities, including its function as a low-calorie sweetener. The three-dimensional configuration of carbohydrates is crucial for elucidating their functional properties. Numerous studies have reported the X-ray crystallographic structures of d-tagatose and its derivatives bearing a free anomeric hydroxy group. However, there are no reports on the X-ray crystallographic structure of d-tagatosides featuring a glycosidic linkage at the anomeric position. In this study, we synthesized methyl α-d-tagatopyranoside from d-tagatose and successfully determined its X-ray crystallographic structure, revealing its ⁵C₂ conformation. Full article

P-glycoprotein (Pgp) plays a significant role in the disposition of cardiac glycoside (CG) drugs across the cell membrane. The relatively narrow therapeutic indices of these drugs, coupled with the co-administration of drugs that inhibit Pgp’s transport mechanism, often cause an increased level of CG in the patient’s plasma, resulting in fatal arrhythmia. Therefore, understanding the underlying mechanism of the CG–Pgp interaction is necessary to circumvent Pgp-mediated transport and effectively design next-generation CGs. In this study, we conducted a comparative analysis to examine the interaction with Pgp and further understand the Pgp-mediated transport of digoxin, digitoxin, digoxigenin, and digitoxigenin. Through the drug-induced kinetic studies of Pgp, our findings suggest that each of the four drugs tested has a single binding site within Pgp. The CG–Pgp binding studies demonstrated that digoxin, digitoxin, and digoxigenin had relatively higher binding affinities. The CG-mediated conformational changes in Pgp indicated that each of the drugs shifts Pgp to an “outward-open” conformation in a nucleotide-dependent manner. STDD NMR indicated that the protons within the δ-lactone ring and the tri-D-digitoxose sugar moieties (glycones) predominantly interact with Pgp. Finally, a model was proposed for CG-induced Pgp-mediated ATP hydrolysis and transport by integrating our data with previously published Pgp-mediated CG transport results. Full article

The escalating global demand for fresh water, driven by urbanization and industrial growth, underscores the need for sustainable water management, particularly in the water-intensive construction sector. Although prior studies have primarily concentrated on treated wastewater, the practical viability of utilizing untreated wastewater has not been thoroughly investigated—especially in developing nations where treatment expenses frequently impede actual implementation, even for non-structural uses. While prior research has focused on treated wastewater, the potential of untreated or partially treated wastewater from diverse industrial sources remains underexplored. This study investigates the feasibility of incorporating wastewater from textile, sugar mill, service station, sewage, and fertilizer industries into concrete paver block production. The novelty lies in a dual approach, combining experimental analysis with XGBoost-based machine learning (ML) models to predict the impact of key physicochemical parameters—such as Biochemical Oxygen Demand (BOD), Chemical Oxygen Demand (COD), and Hardness—on mechanical properties like compressive strength (CS), water absorption (WA), ultrasonic pulse velocity (UPV), and dynamic modulus of elasticity (DME). The ML models showed high predictive accuracy for CS (R² = 0.92) and UPV (R² = 0.97 direct, 0.99 indirect), aligning closely with experimental data. Notably, concrete pavers produced with textile (CP-TXW) and sugar mill wastewater (CP-SUW) attained 28-day compressive strengths of 47.95 MPa and exceeding 48 MPa, respectively, conforming to ASTM C936 standards and demonstrating the potential to substitute fresh water for non-structural applications. These findings demonstrate the viability of using untreated wastewater in concrete production with minimal treatment, offering a cost-effective, sustainable solution that reduces fresh water dependency while supporting environmentally responsible construction practices aligned with SDG 6 (Clean Water and Sanitation) and SDG 12 (Responsible Consumption and Production). Additionally, the model serves as a practical screening tool for identifying and prioritizing viable wastewater sources in concrete production, complementing mandatory laboratory testing in industrial applications. Full article

This study aimed to optimize the enzyme-assisted extraction of polysaccharides (RTFPs) from Rosa roxburghii fruit using response surface methodology. Under the optimal extraction conditions, the yield of RTFPs reached 14.02%, which was close to the predicted value of 13.96%. The primary structural characteristics and the antioxidative and immunomodulatory activities of RTFPs were also examined. Structural characterization revealed that RTFPs comprise 36.38% neutral sugar, 48.83% uronic acid, and 7.29% protein. Their heteropolysaccharide structure features two distinct molecular weight fractions (1.87 × 10⁵ Da and 4.75 × 10³ Da) and a monosaccharide composition dominated by glucose (38.93%), arabinose (20.66%), galactose (20.58%), galacturonic acid (10.94%), and xylose (6.52%). Antioxidant assays demonstrated potent radical scavenging activity, with IC₅₀ values of 11 μg/mL (DPPH) and 150 μg/mL (ABTS), comparable to conventional antioxidants. Immunomodulatory studies on RAW264.7 macrophages revealed that RTFPs (100–400 μg/mL) significantly enhanced phagocytosis by 12.61–76.63% and stimulated the secretion of nitric oxide (NO) and tumor necrosis factor-α (TNF-α). These bioactivities are attributed to RTFPs’ high uronic acid content, moderate molecular weight distribution, unique monosaccharide profile, and highly branched conformation. Full article

Ovalbumin (OVA) and lysozyme (LYZ) are the predominant globular proteins in egg white and play a crucial role in influencing thermal stability and colloidal behavior. In this study, the thermal and conformational stability of OVA and LYZ under various physicochemical conditions including pH (5–9), protein concentrations (5, 10, and 20%), heating rates (2.5, 5, and 10 °C/min), sugars (sucrose and glucose), and salts (NaCl, KCl, and CaCl₂) was systematically investigated using differential scanning calorimetry (DSC), aiming to elucidate their behavior within colloidal and gel-forming systems. The denaturation temperatures (T_d) of OVA and LYZ in water (5% w/v, 5 °C/min) were 80.22 °C and 77.46 °C, respectively. The T_d of LYZ and OVA decreased with protein concentration, heating rate, and CaCl₂. OVA thermal stability was improved with increasing pH, but the stability of LYZ was decreased. Sugars enhanced the thermal stability of OVA and LYZ. In contrast, NaCl and KCl increased OVA stability but reduced LYZ stability. LYZ exhibited nearly 100% reversibility during the second heating cycle in water. Sugars maintained reversibility at approximately 90% for LYZ. However, the presence of salts diminished the reversibility. In contrast, OVA was completely denatured in water and sugar and salt solutions. Full article

Yam (Dioscorea cayennensis subsp. rotundata,hereafter referred to as Dioscorea rotundata) is a staple tropical tuber crop with notable nutritional and economic value. Its development and yield depend on efficient sucrose allocation from source tissues. Sucrose transporters (SUTs), a conserved family of membrane proteins, mediate sucrose loading, translocation, and unloading. Although well-studied in model plants and cereals, SUTs in yam remain largely uncharacterized. This study aims to identify and characterize the SUT gene family in yam and explore their roles in sucrose transport and tuber development. We conducted a genome-wide analysis of yam SUT genes, including gene structure, subcellular localization, and phylogeny. Molecular docking was used to predict sucrose-binding residues, and qRT-PCR assessed gene expression across tissues and tuber developmental stages. Eight SUT genes were identified and classified based on sequence similarity and domain structure. Docking analysis revealed key residues involved in sucrose binding and possible conformational shifts influencing transport. Expression profiling showed that most SUT genes, especially in the tuber apex, were progressively upregulated during development, suggesting roles in sucrose unloading and cell expansion. Additionally, functional validation of DrSUT1 in Arabidopsis thaliana confirmed its involvement in sucrose transport, supporting its role in yam sucrose partitioning. Yam SUT genes, especially those highly expressed in sink tissues, are involved in sucrose partitioning and tuber development. These findings provide structural and functional insights into SUT-mediated sugar transport and lay a foundation for improving sucrose utilization and yield in yam and other tuber crops. Full article

Cacao mucilage is a rich medium for microbial development due to the presence of various sugars, water, pectin, mineral salts, and yeasts of the Saccharomyces cerevisiae type. This study aims to provide added value to this commonly discarded residue, thereby contributing to the economic growth of the Rio Chila area in the Valencia Canton of Los Ríos Province. The methods applied for developing beer consist of malting, grinding, mashing, filtering, boiling, cooling, fermentation (during which cacao mucilage is added), and maturation, followed by physical–chemical analyses. The Fine aroma cacao mucilage presented values of 0.66% acidity, 7.63 °Brix, pH 4.43, absorbance 1.13, transmittance 23.67%, suspended solids 0.04 g: 2.66%, density 1.07 g/mL, turbidity 6.94 NTU, °GL 8.47% vol., foam quantity 1.70 cm, colorimetry L* 50.77, colorimetry a* 18.08, colorimetry b* 50.53, and bitterness degree 39.00. The analyses presented values within the normal parameters applied to beers at the national level (INEN standards). Escherichia coli, Salmonella, and total microorganisms showed no contamination in the microbiological analyses. In the sensory analyses, appearance, aroma, flavour, and mouthfeel were evaluated, with the best experiment being the combination of Fine aroma cacao with a concentration of 30% mucilage and added Cascade hops. This study took into account the concentrations of cacao mucilage (20% and 30%) from the varieties (Fine aroma and CCN-51), as well as the addition of the brewing hops Cascade and Northern Brewer. Regarding the physicochemical characteristics, adding this cacao derivative did not affect craft beer and conformed to the ranges of the NTE INEN 2262 standard. Thus, this research proposes an alternative use for cocoa mucilage, contributing to waste reduction and broadening its potential applications. Full article

Among the various strategies used to enhance the solvation power of supercritical carbon dioxide (scCO₂), the use of CO₂-philic compounds has been extensively studied over the recent two decades. Given the biocompatibility of this medium, extraction technologies based on scCO₂ are particularly attractive, and a molecular-level understanding of intermolecular interactions is crucial for optimizing processing conditions. Functionalized sugars and cyclic oligosaccharides, such as cyclodextrins, can be rendered soluble in scCO₂, opening new avenues for vectorization strategies and supramolecular chemistry in this medium. To support the exploration of CO₂-philic compounds relevant to these research goals, we conducted a molecular dynamics investigation into the solvation properties of cyclodextrins functionalized with CO₂-philic groups. We thoroughly analyzed the key solute–solvent interactions and their influence on the cavity shape. Additionally, we provided insights into the solvation behavior of peracetylated $\alpha$ and $\beta$-glucose across different regions of the carbon dioxide phase diagram. We were able to confirm the importance of the well-known (acetyl)C–O⋯C(CO₂) interaction, as the most important signature of CO₂-philicity of carbonyl compounds. Depending on the substituent, this interaction can be assisted by a cooperative (methyl)₂HCH⋯O(CO₂) intermolecular bond. In cyclodextrins, conformational flexibility, with a possible change in the conformation of some pyranose units, was observed in the macromolecular structure. On the other hand, these structural modifications were not present for $\alpha$- and $\beta$-glucose. Full article

The endocarp of Exocarpium Citri Grandis (ECG) is abundant in various bioactive components, such as polysaccharides; however, there are few studies on them. Thus, it is highly necessary to carry out further research on the structural characterization and biological activities of ECG polysaccharides (EPs), which are important bioactive substances. In this study, water-extracted EPs were precipitated by ethanol with final concentrations of 50%, 70%, and 90% (v/v), respectively. Three crude polysaccharides (EP50, EP70, and EP90) were fractioned successively. The three polysaccharide fractions were structurally elucidated and were investigated in vitro for their biological activities related to glucose metabolism containing inhibitory effects on α-glucosidase and non-enzymatic glycosylation and their antioxidant capacities. The main results are summarized as follows: (1) Gradient ethanol precipitation and physicochemical properties of EPs: The yields of EP50, EP70, and EP90 were 11.18%, 0.57%, and 0.18%, respectively. The total sugar contents were 40.01%, 52.61%, and 53.46%, and the uronic acid contents were 30.25%, 18.11%, and 8.17%, respectively. In addition, the three fractions had the same composition of monosaccharides, including rhamnose, arabinose, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid, with differences in the content of neutral and acidic monosaccharides. They all may be branched polymers and spherical conformation, and they were acidic polysaccharides containing esterified and non-esterified uronic acids, pyranose-form sugars, and glycosidic linkages of α-configuration and β-configuration, with esterification degrees of 32.25%, 28.82%, and 15.58%, respectively. Meanwhile, EP50, EP70, and EP90 were mainly amorphous, and the molecular conformation in solution was a spherical branching polymer without a triple helix structure. The EPs exhibited excellent thermal stability, with their structures remaining stable below 170 °C. (2) In terms of activity research, the results showed that EPs had a good α-glucosidase inhibitory effect with IC₅₀ values of 1.17 mg/mL, 1.40 mg/mL, and 2.72 mg/mL, respectively, among which EP50 was the best. EP50, EP70, and EP90 displayed antioxidant activity by scavenging DPPH and ABTS radicals as well as oxygen radical absorbance capacity. Among them, EP90 had the strongest antioxidant activity. Furthermore, the EPs showed prominent effects on the inhibitory activity of non-enzymatic glycosylation. In summary, the research on the extraction of polysaccharide from ECG provides a technical reference for the further utilization of ECG resources. This study on antioxidant activity provides theoretical support for their use as a natural antioxidant. As oxidation and glycation are relevant to diabetic complications, the result of this work suggests that EPs may be effective in preventing and treating diabetic complications. Full article

The regioselective glycosylation and product specificity of hydroxyflavonoid compounds profoundly influences their biological activity and stability, offering significant therapeutic potential. However, most cyclodextrin glucosyltransferases (CGTases) inherently lack regioselectivity and product specificity for flavone glycosylation. Herein, a CGTase from Paenibacillus macerans was engineered for enhanced glycosylation regioselectivity and product specificity by combining molecular docking analysis and saturation mutagenesis strategies. K232L (favoring 4′-and 6-hydroxyflavones) and K232V (favoring 7-hydroxyflavone) were identified with distinct preferences. In addition, H233Y (preferring for 4′-hydroxyflavones), H233T (preferring for 6′-hydroxyflavones), and H233K (preferring for 7′-hydroxyflavones) also demonstrated distinct regioselectivity. These variants further exhibited enhanced hydrolytic activity, enabling the efficient production of short sugar-chain glycosides. Molecular dynamics (MDs) simulations revealed that the variants adopted optimized catalytic conformations with increased loop region flexibility near the binding pocket, enhancing substrate accessibility. These findings underscore the pivotal roles of K232 and H233 in broadening the substrate scope of CGTase and offer valuable guidance for enzyme engineering targeting regioselective glycosylation. Full article

The demand for intensive agriculture to boost food and crop production has increased. High nitrogen (N) fertilizer use is crucial for increasing agricultural productivity but often leads to significant nitrate losses, posing risks to surface and groundwater quality. This study examines the role of biochar as a soil amendment to enhance nutrient retention and mitigate nitrate leaching. By improving nitrogen efficiency, biochar offers a sustainable strategy to reduce the environmental impacts of intensive agriculture while maintaining soil fertility. An incubation study investigated four biochar feedstocks: spruce bark biochar at 550 °C (SB550), hardwood biochar (75% sugar maple) at 500 °C (HW500), sawdust (fir/spruce) biochar at 427 °C (FS427), and softwood biochar at 500 °C (SW500), to identify the most effective nitrate adsorbent. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR) were employed to analyze biochar morphology and surface functional groups. Adsorption isotherms were modeled using the Langmuir and Freundlich equations. The results indicated that surface functional groups, such as aromatic C=C stretching and bending, aromatic C–H bending, and phenolic O–H bending, play crucial roles in enhancing electrostatic attraction and, consequently, the nitrate adsorption capacity of biochar. The equilibrium adsorption data from this study fit well with both the Langmuir and Freundlich isotherm models. Among the four biochar types tested, SB550 exhibited the highest nitrate adsorption capacity, with a maximum of 184 mg/g. The adsorption data showed excellent conformity to the Langmuir and Freundlich models, with correlation coefficients (R²) exceeding 0.987 for all biochar types. These findings highlight the high accuracy of these models in predicting nitrate adsorption capacities. Full article