Glycosides Research Articles

A polysaccharide from Periplaneta americana promotes macrophage M2 polarization, exhibiting anti-inflammatory and wound-healing activities

A miscellaneous polysaccharide, PAP55–3-1, with a molecular weight of 23.03 kDa, was isolated from Periplaneta americana through extraction with dilute alkali solution, ethanol precipitation, and column chromatography purification. Structural analysis shows that PAP55–3-1 is mainly composed of five monosaccharides: galactosamine hydrochloride, glucosamine hydrochloride, galactose, glucose and mannose. Its main glycosidic bonds are: Manp-(1→, Galp-(1→, →3)-Galp-(1→, →3,6)-Manp-(1→, →2,6)-Manp-(1→, →6)-Manp-(1→, →4)-Galp-(1→, →6-Glcp-(1→, →6)-Galp-(1→, →2)-Manp-(1 →, →3,4)-Glcp-(1→, →3,6)-Galp-(1→. In vitro experiments demonstrated that PAP55–3-1 can effectively inhibit reactive oxygen species (ROS) and O2− production following H2O2−induction. After H2O2−induction, HIF-1α (hypoxia-inducible factor) was translocated in mitochondria PAP55–3-1 increased localization of HIF-1α was located on mitochondria to maintain the stability of mitochondrial function stability, thereby effectively inhibiting H2O2-induced mitochondrial oxidative damage. Additionally, PAP55–3-1 inhibited the M1 polarization of macrophages stimulated by H2O2 and promoted the phenotype polarization of macrophages from M1 to M2, displaying anti-inflammatory and pro-repair properties. In vivo experimental results indicated that PAP55–3-1 promoted wound healing in mice. Immunohistochemical experiments revealed a reduction in CD68 expression and increase in CD206 expression in both positive and the high-dose polysaccharide group control group. This further demonstrated that PAP55–3-1 promotes the phenotype polarization of macrophages from M1 to M2, exerting anti-inflammatory and wound-healing activities.

Phenolic Content, Antioxidant and Antimicrobial Properties of Hawthorn (Crataegus orientalis) Fruit Extracts Obtained via Carbohydrase-Assisted Extraction

The enzyme-assisted approaches for plant phenolics extraction are more eco-friendly methods compared to acid or alkaline hydrolysis. Carbohydrase enzymes can release free phenolics from plant materials by cleaving the glycosidic bonds between phenolic compounds and cell wall polymers. In this study, the efficiency of carbohydrase-assisted treatment approaches was evaluated to extract bioactive phenolics from hawthorn (Crataegus orientalis) fruit residues. Enzymatic treatment of the fruits was operated by using a crude cellulolytic enzyme cocktail from Rhizomucor miehei NRRL 5282 and a pectinase preparate from Aspergillus niger. Both cellulase and combined cellulase–pectinase treatments improved the total phenolic content (TPC) and antioxidant activity of extracts. The TPC increased to 1899 ± 27 mg gallic acid equivalents/100 g dry matter during the combined enzyme treatment, showing a strong correlation with the average antioxidant capacity determined by ferric-reducing antioxidant power (1.7-fold increment) and 2,2-diphenyl-1-picrylhydrazyl (1.15-fold increment) reagents. The major phenolics in enzyme-treated extracts were vanillic and ferulic acids, the concentrations of which increased 115.6-fold and 93.9-fold, respectively, during carbohydrase treatment. The planktonic growth of Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Chromobacterium violaceum was slightly inhibited by the extracts with minimum inhibitory concentration values between 15.0 and 77.9 mg/mL, while the yeasts tested were quite resistant to the samples. B. subtilis and yeast biofilms were sensitive to the enzyme-treated extracts, which also showed quorum-sensing inhibitory effects against C. violaceum. The obtained bioactive hawthorn extracts hold potential as a natural source of antioxidants and antimicrobials.

Structural Characterization and Antioxidant Activity of Exopolysaccharide Produced from Beet Waste Residue by Leuconostoc pseudomesenteroides

Lactic acid bacteria exopolysaccharide (EPS) is a large molecular polymer produced during the growth and metabolism of lactic acid bacteria. EPS has multiple biological functions and is widely used in fields such as food and medicine. However, the low yield and high production cost of EPS derived from lactic acid bacteria limit its widespread application. In this study, we used beet waste residue as a substrate to produce EPS by fermentation with Leuconostoc pseudomesenteroides to improve the utilization rate of agricultural waste and reduce the production cost of lactic acid bacterial EPS. After purification, the molecular weight (Mw) of EPS was determined to be 417 kDa using high-performance size exclusion chromatography (HPSEC). High-performance liquid chromatography (HPLC), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy revealed that the EPS was composed of glucose subunits with α-1,6 glycosidic linkages. The thermal analysis and heavy metal adsorption capacity revealed a relatively high degradation temperature of 315.54 °C and that the material could effectively adsorb Cu2+. Additionally, the findings indicated that the EPS exhibited a significant ability to neutralize free radicals, a property that was found to be concentration dependent. Furthermore, the results of the intracellular study showed the protective effect of freshly isolated EPS on tBHP-induced cellular oxidative stress at a concentration of 50 µg/mL. These results suggest that the EPS from L. pseudomesenteroides may be developed as antioxidant agents for functional food products and pharmaceutical applications due to its capacity to scavenge free radicals.

Crystal structures of Aspergillus oryzae exo-β-(1,3)-glucanase reveal insights into oligosaccharide binding, recognition, and hydrolysis.

Exo-β-(1,3)-glucanases are promising enzymes for use in the biofuel industry as they hydrolyse sugars such as laminarin, a major constituent of the algal cell wall. This study reports structural and biochemical characterizations of Aspergillus oryzae exo-β-(1,3)-glucanase (AoBgl) belonging to the GH5 family. Purified AoBgl hydrolyses β-(1,3)-glycosidic linkages of the oligosaccharide laminaritriose and the polysaccharide laminarin effectively. We have determined three high-resolution structures of AoBgl: (a) the apo form at 1.75 Å, (b) the complexed form with bound cellobiose at 1.73 Å and (c) the glucose-bound form at 1.20 Å. The crystal structures, molecular dynamics simulation studies and site-directed mutagenesis reveal the mode of substrate binding and interactions at the active site. The results also indicate that AoBgl effectively hydrolyses trisaccharides and higher oligosaccharides. The findings from our structural and biochemical studies would aid in rational engineering efforts to generate superior AoBgl variants and similar GH5 enzymes for their industrial use.

In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides.

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet. The abundances of 3 of 15 Bacteroides strains increased, most prominently B. intestinalis. Underlying mechanisms were characterized by analyzing in vivo expression of the carbohydrate utilization machinery, using retrievable microscopic paramagnetic particles with bound SG oligosaccharides and assaying SG degradation by individual purified B. intestinalis glycoside hydrolases. The results reveal that SGs can selectively co-opt carbohydrate utilization machinery in different human gut Bacteroides and demonstrate a means for identifying artificial carbohydrate structures for targeted bacterial manipulation.

A Comparative Analysis of Milk Oligosaccharides via LC-MS: Globally Distributed Cattle Breeds and Native Northern Finncattle

Milk oligosaccharides are complex carbohydrates composed of various monosaccharide units linked together by glycosidic bonds. They play an essential role in promoting gut health by fostering beneficial bacteria, supporting the development of the immune system, and protecting against infections and diseases. This work compared the oligosaccharide profiles in widely utilized breeds such as Holstein and Ayrshire (Nordic Red), with the native Northern Finncattle, which is considered an endangered breed. Oligosaccharides were extracted from milk and analyzed by liquid chromatography–mass spectrometry. The composition and relative abundance of the identified oligosaccharides were characterized and compared. The statistical analyses showed that neutral, sialylated, and fucosylated oligosaccharides vary among the breeds. Ayrshire and Northern Finncattle oligosaccharides formed a cluster, while Holstein’s profile shared features with both Ayrshire and Northern Finncattle. Holstein had the lowest abundance of fucosylated OS among the three breeds, with Ayrshire having the highest content followed by Northern Finncattle. The relatively higher sialylated over neutral content of Northern Finncattle is an important feature that should be preserved. Ayrshire is a good candidate to recover more diverse oligosaccharides with potential gut health implications for consumers.

Unveiling a novel exopolysaccharide produced by Pseudomonas alcaligenes Med1 isolated from a Chilean hot spring as biotechnological additive

Exopolysaccharides (EPSs), a constitutive part of bacterial biofilm, act as a protecting sheath to the extremophilic bacteria and are of high industrial value. In this study, we elucidate a new EPS produced by thermotolerant (growth from 34–44 °C) strain Pseudomonas alcaligenes Med1 from Medano hot spring (39.1 °C surface temperature, pH 7.1) located in the Central Andean Mountains of Chile. Bacterial growth was screened for temperature tolerance (10–60 °C) to confirm the thermotolerance behaviour. Physicochemical properties of the EPS were characterized by different techniques: Scanning Electron Microscopy- Energy Dispersive X-ray Spectroscopy (SEM-EDS), Atomic Force Microscopy (AFM), High-Performance Liquid Chromatography (HPLC), Gel permeation chromatography (GPC), Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), and Thermogravimetric analysis (TGA). Whole genome of P. alcaligenes Med1 has also been studied in detail to correlate the structural and functional characteristics with genomic insight. The EPS demonstrated amorphous surface roughness composed of evenly distributed macromolecular lumps composed of mainly carbon and oxygen. The monosaccharide analysis has shown the presence of glucose, galactose, and mannose sugars at different ratios. TGA revealed the high thermal stability (315.3 °C) of the polysaccharide. The GPC has shown that Med1 is a low molecular weight polysaccharide (34.8 kDa) with low PI. The 2D-NMR linkage analysis suggests a diverse array of glycosidic bonds within the exopolysaccharide structure. The functional properties of the EPS were evaluated for food industry applications, specifically for antioxidant (DPPH, FRAP an H2O2). Extracted Med1 EPS revealed significant emulsification activity against different food grade vegetative oils (Coconut oil, Corn oil, Canola oil, Avocado oil, Sunflower oil, Olive oil, and Sesame oil). The highest 33.9% flocculation activity was observed with 60 mg L−1 EPS concentration. It showed water-holding (WHC) of 107.6% and oil-holding (OHC) capacity of 110.8%. The functional EPS produced by Pseudomonas alcaligenes Med1 from Central Andean Chilean hot spring of central Chile can be a useful additive for the food-processing industry.

Molecular Structure and Properties of Resistant Dextrins from Potato Starch Prepared by Microwave Heating.

The dextrinization of potato starch was performed using a sophisticated single-mode microwave reactor with temperature and pressure control using 10 cycles of heating with stirring between cycles. Microwave power from 150 to 250 W, a cycle time from 15 to 25 s, and two types of vessels with different internal diameters (12 and 24 mm) and therefore different thicknesses of the heated starch layer were used in order to estimate the impact of vessel size used for microwave dextrinization. The characteristics of resistant dextrins (RD) including solubility in water, total dietary fiber (TDF) content, color parameters, the share of various glycosidic bonds, and pasting and rheological properties were carried out. The applied conditions allowed us to obtain RDs with water solubility up to 74% at 20 °C, as well as TDF content up to 47%, with a predominance of low-molecular-weight soluble fiber fraction, with increased content of non-starch glycosidic bonds, negligible viscosity, and a slightly beige color. The geometry of the reaction vessel influenced the properties of dextrins obtained under the same heating power, time, and repetition amounts. Among the conditions used, the most favorable conditions were heating 10 times for 20 s at 200 W in a 10 mL vessel and the least favorable were 15 s cycles.

Chemical Synthesis of Conjugation-Ready Trisaccharides Corresponding to Biological Repeating Units of Pseudomonas aeruginosa Serotype 10 and 19 O-Antigens.

Here we report the chemical synthesis of conjugation-ready trisaccharides, representing biological repeating units of Pseudomonas aeruginosa serotype 10 and 19 O-antigens. The α-d-QuiN3 glycosidic bond was stereoselectively synthesized through TMSI─Ph3P═O mediated 1,2-cis glycosylation. Selective oxidation of the C6-OH group at the disaccharide stage allowed for benzylidene-promoted construction of the α-l-GalN3 glycosidic bond and simplification of the postglycosylation process at the trisaccharide stage. The low reaction temperature and neighboring electron-donating effect facilitated the efficient synthesis of the trisaccharide.

Comparative Bindings of Glycosaminoglycans with CXCL8 Monomer and Dimer: Insights from Conformational Dynamics and Kinetics of Hydrogen Bonds.

GAGs bind to both the monomeric and dimeric forms of CXCL8, helping to form a concentration gradient of the chemokine that facilitates the recruitment of neutrophils to an injury site and supports other biological functions. In this study, atomistic molecular dynamics simulations were conducted to investigate the binding behavior of two hexameric GAGs sulfated at two different positions, chondroitin sulfate (CS) and heparan sulfate (HS), with the monomer (SIL8) and dimer (DIL8) forms of the CXCL8 protein. The results support that the conformational diversity of CS and HS appeared to be more when binding with monomer SIL8 than dimer DIL8. CS gained more configurational entropy from glycosidic linkage flexibility when bound to SIL8 than DIL8, with a higher energy barrier, whereas HS exhibited a lower energy barrier for configurational entropy when bound to SIL8 and DIL8. The monomer SIL8 exhibited more favorable and preferential binding with GAGs compared to DIL8. Formation of hydrogen bonds with the basic amino acids of SIL8 and GAG was more rigid and required higher activation energy to break than the other identified hydrogen bondings. Water molecules involved in hydrogen bonding with GAGs, excluding those with basic amino acids of DIL8, showed longer lifetimes and slower relaxation compared to SIL8. This suggests that water-mediated interactions also favor binding of DIL8 with GAGs. Despite having more basic amino acids, DIL8 did not display stronger binding than SIL8, indicating the significant role of basic residues in stabilizing the GAG-protein interactions in the monomers. The reason could be that the greater number of nonbasic amino acids in dimeric CXCL8 stabilizes the complex by forming water-mediated hydrogen bonds, reducing the conformational preferences for binding with GAGs. In contrast, the monomeric form of CXCL8 exhibits a higher conformational preference for protein-GAG interactions.

Limosilactobacillus reuteri DSM 17938 Produce Bioactive Components during Formulation in Sucrose.

Improved efficacy of probiotics can be achieved by using different strategies, including the optimization of production parameters. The impact of fermentation parameters on bacterial physiology is a frequently investigated topic, but what happens during the formulation, i.e., the step where the lyoprotectants are added prior to freeze-drying, is less studied. In addition to this, the focus of process optimization has often been yield and stability, while effects on bioactivity have received less attention. In this work, we investigated different metabolic activities of the probiotic strain Limosilactobacillus reuteri DSM 17938 during formulation with the freeze-drying protectant sucrose. We discovered that the strain consumed large quantities of the added sucrose and produced an exopolysaccharide (EPS). Using NMR, we discovered that the produced EPS was a glucan with α-1,4 and α-1,6 glycosidic bonds, but also that other metabolites were produced. The conversion of the lyoprotectant is hereafter designated lyoconversion. By also analyzing the samples with GCMS, additional potential bioactive compounds could be detected. Among these were tryptamine, a ligand for the aryl hydrocarbon receptor, and glycerol, a precursor for the antimicrobial compound reuterin (3-hydroxypropionaldehyde). To exemplify the bioactivity potential of lyoconversion, lyoconverted samples as well as purified EPS were tested in a model for immunomodulation. Both lyoconverted samples and purified EPS induced higher expression levels of IL-10 (2 times) and IL-6 (4-6 times) in peripheral blood mononuclear cells than non-converted control samples. We further found that the initial cultivation of DSM 17938 with sucrose as a sugar substrate, instead of glucose, improved the ability to convert sucrose in the lyoprotectant into EPS and other metabolites. Lyoconversion did not affect the viability of the bacteria but was detrimental to freeze-drying survival, an issue that needs to be addressed in the future. In conclusion, we show that the metabolic activities of the bacteria during the formulation step can be used as a tool to alter the activity of the bacteria and thereby potentially improve probiotic efficacy.

Structural characterization, antioxidant and immunomodulatory activities of a polysaccharide from a traditional Chinese rice wine, Guangdong Hakka Huangjiu

Hakka Huangjiu, a traditional Chinese rice wine, boasts a rich history and is known for its immunomodulatory, antibacterial, anti-aging and anti-fatigue effects. However, there is limited research on the primary active components and molecular mechanism of the bioactivity of Hakka Huangjiu. To address this gap, this study assessed the structural characteristics, antioxidant, and immunomodulatory activities of the polysaccharide-1 of Guangdong Hakka Huangjiu (HP1). Structural analysis revealed that HP1 had a low molecular weight polysaccharide of 5550 Da, primarily consisting of glucose (93.2 %), with smaller amounts of xylose, mannuronic acid and galactose. Methylation and NMR analysis suggested that the main glycosidic linkages present in HP1 are α-D-Glcp-(1→, →4)-α-D-Glcp-(1 → and →6) -α-D-Glcp-(1→. Furthermore, HP1 exhibited dose-dependent DPPH·, ABTS+ and OH· scavenging activity. HP1 exhibited significant protection of HepG2 cells from H2O2 damage. Additionally, HP1 induced the release of NO, TNF-α, IL-6 and iNOS in RAW264.7 cells. HP1 treatment significantly increased mRNA expression of TNF-α, IL-6, iNOS, COX-2, IL-1β and TGF-β1. These results suggested that polysaccharides HP1 may have potential as a novel natural antioxidant and immunomodulatory product for use in nutraceuticals and functional foods.

Microbial Polysaccharides as Functional Components of Packaging and Drug Delivery Applications.

This review examines microbial polysaccharides' properties relevant to their use in packaging and pharmaceutical applications. Microbial polysaccharides are produced by enzymes found in the cell walls of microbes. Xanthan gum, curdlan gum, pullulan, and bacterial cellulose are high-molecular-weight substances consisting of sugar residues linked by glycoside bonds. These polysaccharides have linear or highly branched molecular structures. Packaging based on microbial polysaccharides is readily biodegradable and can be considered as a renewable energy source with the potential to reduce environmental impact. In addition, microbial polysaccharides have antioxidant and prebiotic properties. The physico-chemical properties of microbial polysaccharide-based films, including tensile strength and elongation at break, are also evaluated. These materials' potential as multifunctional packaging solutions in the food industry is demonstrated. In addition, their possible use in medicine as a drug delivery system is also considered.

A Neutral Polysaccharide from Medicago Sativa L.: Structural Properties and Hypoglycemic Activity In Vitro and In Vivo.

Medicago sativa polysaccharides (MSPs) are beneficial compounds extracted from Medicago sativa L. that exhibit multiple medicinal activities. However, little is known about their hypoglycemic effects. In this study, MSP-II-a, a neutral polysaccharide with an Mw of 4.3×104 Da, was isolated and purified from M. sativa L. Monosaccharide composition analysis determined that MSP-II-a was composed of arabinose, glucose, galactose, mannose, rhamnose, and xylose in a molar ratio of 2.1 : 4.0 : 1.1:0.4 : 1.4 : 1.1. Structural characterization of MSP-II was performed using a combination of methylation analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results showed that MSP-II-a was mainly comprised of 1,4-p-Glc, 1,3,4-Rha, and 1,3-p-Gal glycosidic linkages, revealing a mesh-like texture with irregular blade shapes. In vitro assays demonstrated that MSP-II-a, at concentrations of 200 and 400 μg/mL, promoted glucose uptake in insulin-resistant 3T3-L1 adipocytes. In vivo studies have shown that MSP-II-a significantly alleviates insulin resistance by reducing fasting blood glucose levels and increasing hepatic glycogen synthesis in HFD/STZ-induced diabetic mice. These findings revealed that MSP-II-a is a promising source of bioactive polysaccharides with potential hypoglycemic activity.

Characterization of Unfractionated Polysaccharides in Brown Seaweed by Methylation-GC-MS-Based Linkage Analysis.

This study introduces a novel approach to analyze glycosidic linkages in unfractionated polysaccharides from alcohol-insoluble residues (AIRs) of five brown seaweed species. GC-MS analysis of partially methylated alditol acetates (PMAAs) enables monitoring and comparison of structural variations across different species, harvest years, and tissues with and without blanching treatments. The method detects a wide array of fucose linkages, highlighting the structural diversity in glycosidic linkages and sulfation position in fucose-containing sulfated polysaccharides. Additionally, this technique enhances cellulose quantitation, overcoming the limitations of traditional monosaccharide composition analysis that typically underestimates cellulose abundance due to incomplete hydrolysis of crystalline cellulose. The introduction of a weak methanolysis-sodium borodeuteride reduction pretreatment allows for the detection and quantitation of uronic acid linkages in alginates.

Discovery of glycosidated glycyrrhetinic acid derivatives: Natural product-based soluble epoxide hydrolase inhibitors

There are few reports on soluble epoxide hydrolase (sEH) structure-activity relationship studies using natural product-based scaffolds. In this study, we discovered that C-30 urea derivatives of glycyrrhetinic acid such as 33, rather than C-20/C-3 urea derivatives, possess in vitro sEH inhibitory capabilities. Furthermore, we explored the impact of stereoconfigurations at C-3 and C-18 positions, and glycosidic bonds at the 3-OH on the compound's activity. Consequently, a glycoside of 33, specifically 49Cα containing alpha-oriented mannose, exhibited promising in vivo efficacy in alleviating carrageenan-induced paw edema and acetic acid-induced writhing. Meanwhile, 49Cα demonstrated potential in mitigating acute pancreatitis by modulating the ratios of anti-inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory dihydroxyeicosatrienoic acids (DHETs). The co-crystal structure of sEH in complex with 49Cα revealed that the N-tetrahydropyranylmethylene urea hydrogen bonded with the residues within the sEH tunnel, contrasting with the mannose component that extended beyond the tunnel's confines. Our findings highlight 49Cα (coded LQ-38) as a promising candidate for anti-inflammatory and analgesic effects, and pave the way for the future rational design of triterpenoid-based sEH inhibitors.

Sodium alginate-g-polyacrylamide hydrogel for water retention and plant growth promotion in water-deficient soils

Natural polymer-based hydrogels are preferred as soil water retention agents due to their inherent biocompatibility and biodegradability. Generally, these natural polymers are chemically modified by graft polymerization of vinyl monomers to improve their water absorption and retention properties. Among the polysaccharides used to prepare natural hydrogels, those based on sodium alginate (Alg) stand out for their high-water absorption and retention capacity, as well as for their ability to promote plant growth. The main objective of this study was to develop a biodegradable alginate-based hydrogel as a water retainer to promote plant growth under water deficit conditions. The synthesis was achieved by grafting poly(acrylamide) (PAM) onto Alg backbone, using bisacrylamide as chemical crosslinker and different ratios of alginate:acrylamide (Ac). In addition, Eucalyptus nitens seedlings were used as a model plant to evaluate the effect of alginate-g-polyacrylamide (Alg:PAM) hydrogel application to the growing medium on plant survival, growth, and physiological responses under both well-watered and water-deficient soil conditions. The maximum degree of swelling (65 g/g) was obtained for the hydrogel prepared. The pseudo-second order model described the water uptake kinetics of the hydrogel. The degradability of Alg:PAM hydrogel reached up to 85 % in 5 weeks in soil and occurs by breaking the glycosidic bonds of the alginate. The E. nitens seedlings cultivated with different doses of Alg:PAM hydrogel (4:1 Alg:Ac) showed higher values of height and root diameter relative growth, survival and photosynthetic responses in comparison to non-treated plants. The results indicate that Alg:PAM hydrogel (4:1 Alg:Ac) has promising applications in forestry as a water retention and seedling growth promoter under water deficient conditions.

Inhibitory Effects on RNA Binding and RNase H Induction Activity of Prodrug-Type Oligodeoxynucleotides Modified with a Galactosylated Self-Immolative Linker Cleavable by β-Galactosidase.

Prodrug-type oligonucleotides (prodrug-ONs) are a class of oligonucleotide designed for activation under specific intracellular conditions or external stimuli. Prodrug-ONs can be activated in the target tissues or cells, thereby reducing the risk of adverse effects. In this study, we synthesized prodrug-type oligodeoxynucleotides activated by β-galactosidase, an enzyme that is overexpressed in cancer and senescent cells. These oligodeoxynucleotides (ODNs) contain a modified thymidine conjugated with galactose via a self-immolative linker at the O4-position. UV-melting analysis revealed that the modifications decreased the melting temperature (Tm) compared with that of the unmodified ODN when hybridized with complementary RNA. Furthermore, cleavage of the glycosidic bond by β-galactosidase resulted in the spontaneous removal of the linker from the nucleobase moiety, generating unmodified ODNs. Additionally, the introduction of multiple modified thymidines into ODNs completely inhibited the RNase H-mediated cleavage of complementary RNA. These findings suggest the possibility of developing prodrug-ONs, which are specifically activated in cancer cells or senescent cells with high β-galactosidase expression.

The Characteristics Analysis of Hyaluronic Acid Modified By Cold Atmospheric Plasma and Its Performance in Hydrogel Preparation

ABSTRACTHyaluronic acid (HA) is extensively utilized in biomedical applications, and its functionality can be enhanced by introducing aldehyde groups (─CHO) through oxidation. In this study, cold atmospheric plasma (CAP) was used to treat aqueous HA solutions, resulting in the formation of plasma‐modified HA (PMHA) containing ─CHO groups. The free radicals generated from interactions between water molecules and CAP particles reacted with HA, leading to the oxidation of hydroxyl groups into ─CHO and the cleavage of glycosidic bonds, causing molecular depolymerization. The PMHA was then used to synthesize hydrogels in combination with carboxymethyl chitosan and ɛ‐polylysine. This study presents an effective approach for generating HA with aldehyde functionalities and offers insights into the interaction between CAP and polysaccharides.

ZnI2-Mediated cis-Glycosylations of Various Constrained Glycosyl Donors: Recent Advances in cis-Selective Glycosylations.

An efficient and versatile glycosylation methodology is crucial for the systematic synthesis of oligosaccharides and glycoconjugates. A direct intermolecular and an indirect intramolecular methodology have been developed, and the former can be applied to the synthesis of medium-to-long-chain glycans like that of nucleotides and peptides. The development of a generally applicable approach for the stereoselective construction of glycosidic bonds remains a major challenge, especially for the synthesis of 1,2-cis glycosides such as β-mannosides, β-L-rhamnosides, and β-D-arabinofuranosides with equatorial glycosidic bonds as well as α-D-glucosides with axial ones. This review introduces the direct formation of cis-glycosides using ZnI2-mediated cis-glycosylations of various constrained glycosyl donors, as well as the recent advances in the development of stereoselective cis-glycosylations.