Search Results (63)

Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming inclusion complexes with various guest molecules, enhancing solubility, stability, and bioavailability. This review outlines the structural features of native CDs and their chemically modified derivatives, emphasizing the influence of functionalization on host–guest interactions. Synthetic approaches for CD derivatization are summarized, with attention to recent developments in stimuli-responsive systems and targeted drug delivery. Analytical techniques commonly employed for characterizing CD complexes, such as spectroscopy, thermal analysis, and molecular modeling, are briefly reviewed. Applications in pharmaceutical formulations are discussed, including inclusion complexes, CD-based conjugates, and nanocarriers designed for solubility enhancement, controlled release, and site-specific delivery. Special consideration is given to emerging multifunctional platforms with biomedical relevance. The regulatory status of CDs is addressed, with reference to FDA- and EMA-approved formulations. Safety profiles and toxicological considerations associated with chemically modified CDs, particularly for parenteral use, are highlighted. This review presents an integrative perspective on the design, characterization, and application of CD-based systems, with a focus on translational potential and current challenges in pharmaceutical development. Full article

Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) are powerful techniques that have been employed to analyze foodstuffs comprehensively. These techniques offer in-depth information about the chemical composition, structure, and spatial distribution of components in a variety of food products. Quantitative NMR is widely applied for precise quantification of metabolites, authentication of food products, and monitoring of food quality. Low-field ¹H-NMR relaxometry is an important technique for investigating the most abundant components of intact foodstuffs based on relaxation times and amplitude of the NMR signals. In particular, information on water compartments, diffusion, and movement can be obtained by detecting proton signals because of H₂O in foodstuffs. Saffron adulterations with calendula, safflower, turmeric, sandalwood, and tartrazine have been analyzed using benchtop NMR, an alternative to the high-field NMR approach. The fraudulent addition of Robusta to Arabica coffee was investigated by ¹H-NMR Spectroscopy and the marker of Robusta coffee can be detected in the ¹H-NMR spectrum. MRI images can be a reliable tool for appreciating morphological differences in vegetables and fruits. In kiwifruit, the effects of water loss and the states of water were investigated using MRI. It provides informative images regarding the spin density distribution of water molecules and the relationship between water and cellular tissues. ¹H-NMR spectra of aqueous extract of kiwifruits affected by elephantiasis show a higher number of small oligosaccharides than healthy fruits do. One of the frauds that has been detected in the olive oil sector reflects the addition of hazelnut oils to olive oils. However, using the NMR methodology, it is possible to distinguish the two types of oils, since, in hazelnut oils, linolenic fatty chains and squalene are absent, which is also indicated by the ¹H-NMR spectrum. NMR has been applied to detect milk adulterations, such as bovine milk being spiked with known levels of whey, urea, synthetic urine, and synthetic milk. In particular, T2 relaxation time has been found to be significantly affected by adulteration as it increases with adulterant percentage. The ¹H spectrum of honey samples from two botanical species shows the presence of signals due to the specific markers of two botanical species. NMR generates large datasets due to the complexity of food matrices and, to deal with this, chemometrics (multivariate analysis) can be applied to monitor the changes in the constituents of foodstuffs, assess the self-life, and determine the effects of storage conditions. Multivariate analysis could help in managing and interpreting complex NMR data by reducing dimensionality and identifying patterns. NMR spectroscopy followed by multivariate analysis can be channelized for evaluating the nutritional profile of food products by quantifying vitamins, sugars, fatty acids, amino acids, and other nutrients. In this review, we summarize the importance of NMR spectroscopy in chemical profiling and quality assessment of food products employing magnetic resonance technologies and multivariate statistical analysis. Full article

Prebiotic oligosaccharides have attracted significant interest in dermatology and skin health due to their ability to modulate the skin microbiome and microbiota–host interactions. This review offers a novel dual perspective, systematically examining the benefits of both oral intake and topical application of prebiotic oligosaccharides, including well-established prebiotics (e.g., human milk oligosaccharides, galacto- and fructo-oligosaccharides) and emerging prebiotic candidates (e.g., gluco-oligosaccharides, chitosan-oligosaccharides, agaro-oligosaccharides). First, cutting-edge synthetic processes for producing diverse oligosaccharides and their structural chemistry are introduced. Then, we discuss in vitro studies demonstrating their efficacy in promoting skin commensals, inhibiting pathogens, and conferring protective effects, such as antioxidant, anti-inflammatory, anti-melanogenic, and wound-healing properties. Furthermore, we emphasize in vivo animal studies and clinical trials revealing that prebiotic oligosaccharides, administered orally or topically, alleviate atopic dermatitis, enhance skin hydration, attenuate acne, and protect against photo-aging by modulating skin–gut microbiota and immune responses. Mechanistically, we integrate genetic and molecular insights to elucidate how oligosaccharides mediate these benefits, including gut–skin axis crosstalk, immune regulation, and microbial metabolite signaling. Finally, we highlight current commercial applications of oligosaccharides in cosmetic formulations while addressing scientific and practical challenges, such as structure–function relationships, clinical scalability, and regulatory considerations. This review bridges mechanistic understanding with practical applications, offering a comprehensive resource for advancing prebiotic oligosaccharides-based skincare therapies. Full article

Specific monosaccharide residue, β-D-galactofuranose (Galf) featuring a five-membered ring structure, is found in the glycans of fungi and bacteria, but is normally absent in healthy mammals and humans. In this study, synthetic oligosaccharides mimicking bacterial and fungal glycans were investigated by SERS (Surface-Enhanced Raman Scattering) techniques for the first time to distinguish between different types of glycan chains. SERS spectra of oligosaccharides related to fungal α-(1→2)-mannan, β-(1→3)-glucan, β-(1→6)-glucan, galactomannan of Aspergillus, galactan I of Klebsiella pneumoniae, and diheteroglycan of Enterococcus faecalis were measured. To analyze the spectra, a number of machine learning methods were used that complemented each other: principal component analysis (PCA), confidence interval estimation (CIE), and logistic regression with L1 regularization. Each of the methods has shown own effectiveness in analyzing spectra. Namely, PCA allows the visualization of the divergence of spectra in the principal component space, CIE visualizes the degree of overlap of spectra through confidence interval analysis, and logistic regression allows researchers to build a model for determining the belonging of the analyte to a given class of carbohydrate structures. Additionally, the methods complement each other, allowing the determination of important features representing the main differences in the spectra containing and not containing Galf residue. The developed mathematical models enabled the reliable identification of Galf residues within glycan compositions. Given the high sensitivity of SERS, this spectroscopic technique serves as a promising basis for developing diagnostic test systems aimed at detecting biomarkers of fungal and bacterial infections. Full article

Oligosaccharides and glycoconjugates play essential roles in various biological processes such as cellular recognition and signaling, and thus have attracted tremendous attention in the synthetic and biological communities over the past few decades. Contributing to this field, we have achieved the synthesis of the aminoxyglycoside pentasaccharide subunit of Pseudomonas aeruginosa polysaccharide synthesis locus (Psl) exopolysaccharide through an efficient 23 step process. This pentasaccharide was designed with an aminooxy derivative at the reducing end, which was used in a 2-step oxime-based bioconjugation to the protein carrier CRM197, with an epitope ratio of 1:4. The conjugate vaccine could generate anti-Psl antibodies that could recognize P. aeruginosa PAO1 bacteria and initiate opsonophagocytic killing of the bacteria. In addition, the aminoxyglycoside could be conveniently conjugated to a bifunctional aldehyde-biotin reagent, which can be used for quantifying antibody titers in vaccination studies. Full article

In previous quests to synthesize fragments of tumor-associated carbohydrate antigens (TACAs), we determined that bromoalkyl β glycosides of N-acetylglucosamine were labile and incompatible with some of the synthetic conditions required for the preparation of oligosaccharides. While N-acetylglucosamine chloroalkyl β glycosides are common intermediates for oligosaccharide synthesis, they exhibit poor yields upon subsequent reactions used to introduce the oxyamine required for further conjugation. Thus, we looked to synthesize these TACAs using chloroalkyl β glycosides and substitute the chlorine for bromine at a later synthetic stage. Upon substitution of the bromine for chlorine using sodium bromide in a dibromomethane (DBM) dimethylformamide (DMF) mixture, we observed the unexpected anomerization of the N-acetylglucosamine β glycosides, yielding up to 90% of the α glycosides. We describe our studies of this unexpected anomerization and report on how the anomeric ratios can be controlled experimentally. Interestingly, we also report the anomerization of alkyl β glycosides of N-acetylglucosamine in a mixture of DBM and DMF without sodium bromide. Further studies are being conducted to determine the mechanism of this anomerization and the scope of this reaction. Full article

(1) Background: Toll-like receptor 2 (TLR2) on platelets is increasingly recognized as a pivotal mediator in infection-induced platelet activation and aggregation, contributing to both inflammatory and thrombotic diseases. Targeting TLR2 on platelets offers a promising therapeutic strategy for inflammatory and thrombotic-related disorders. However, inhibitors targeting platelet TLR2 have not yet been reported. (2) Methods: Platelet aggregation was assessed using a light transmission aggregometer. Platelet activation was evaluated by measuring the release of P-selectin and von Willebrand factor (vWF) via ELISA. Intracellular Ca²⁺ mobilization was quantified using Fluo 3-AM fluorescence, recorded by flow cytometry. Static platelet adhesion was visualized under a microscope, and the formation of platelet–granulocyte aggregates in human whole blood was analyzed by flow cytometry. (3) Results: Fucosylated glycosaminoglycan (FG) tetradecasaccharide HS14 inhibited the activation and aggregation of human platelets induced by the synthetic bacterial lipopeptide Pam3CSK4 in a concentration-dependent manner. This inhibitory effect gives rise to significant anti-inflammatory and anti-thrombotic activities, as evidenced by reduced platelet adhesion and decreased platelet–granulocyte aggregates formation in human whole blood. (4) Conclusions: This study is the first to identify FG oligosaccharide HS14 as a promising inhibitor of platelet TLR2/TLR1, demonstrating significant therapeutic potential for inflammatory and thrombotic-related diseases. Full article

Fluorination of carbohydrates is a promising strategy to produce glycomimetics with improved pharmacological properties, such as increased metabolic stability, bioavailability and protein-binding affinity. Fluoroglycans are not only of interest as inhibitors and chemical probes but are increasingly being used to develop potential synthetic vaccine candidates for cancer, HIV and bacterial infections. Despite their attractiveness, the synthesis of fluorinated oligosaccharides is still challenging, emphasizing the need for efficient protocols that allow for the site-specific incorporation of fluorine atoms (especially at late stages of the synthesis). This is particularly true for the development of fully synthetic vaccine candidates, whose (modified) carbohydrate antigen structures (glycotopes) per se comprise multistep synthesis routes. Based on a known minimal protective epitope from the capsular polysaccharide of S. pneumoniae serotype 8, a panel of six novel F-glycotope mimetics was synthesized, equipped with amine linkers for subsequent conjugation to immunogens. Next to the stepwise assembly via fluorinated building blocks, the corresponding 6F-substituted derivatives could be obtained by microwave-assisted, nucleophilic late-stage fluorination of tri- and tetrasaccharidic precursors in high yields. The described synthetic strategy allowed for preparation of the targeted fluorinated oligosaccharides in sufficient quantities for future immunological studies. Full article

The ability to recognize hidden symmetry in a highly asymmetric world is a key factor in how we view and understand the world around us. Despite the fact that it is an intrinsic property of the natural world, we have an innate ability to find hidden symmetry in asymmetric objects. The inherent asymmetry of the natural world is a fundamental property built into its chemical building blocks (e.g., proteins, carbohydrates, etc.). This review highlights the role of asymmetry in the structure of the carbohydrates and how these stereochemical complexities present synthetic challenges. This survey starts with an overview of the role synthetic chemistry plays in the discovery of carbohydrates and their 3D structure. This review then introduces various de novo asymmetric synthetic approaches that have been developed for the synthesis of carbohydrates and, in particular, oligosaccharides. The two most successful strategies for oligosaccharide synthesis rely on diastereoselective palladium-catalyzed glycosylation. The first uses an Achmatowicz reaction to asymmetrically prepare pyranose building blocks along with a substrate-controlled Pd-glycosylation. The other strategy couples a ligand-controlled Pd-glycosylation with a ring-closing metathesis for oligosaccharide assembly. Full article

Bovine brucellosis (bB) is a zoonosis mainly caused by the Brucella abortus species in cattle. Bovine brucellosis can present with either a range of clinical symptoms, including spontaneous abortions in the last trimester of pregnancy, retained fetal membranes, and decreased milk production, or it can be asymptomatic. In Ecuador, vaccination against bB with S19 and/or RB51 is not mandatory and is the responsibility of the farmer. As serology is a convenient method for detecting antibodies against Brucella, evaluating the diagnostic performance and discriminative ability of such tests in various epidemiological settings is required. To estimate and compare the diagnostic sensitivity (Se) and specificity (Sp) of two screening tests, a new competitive (cELISA) and an indirect ELISA based on a new synthetic antigen (iELISA), a randomized, stratified, cross-sectional, serological survey was performed on the cattle population (3299 bovine sera from 223 farms) in continental Ecuador. A Bayesian approach was used to evaluate the two tests by estimating their respective diagnostic Se and Sp, as well as the true prevalence of bB in different sub-populations (non-vaccinated, vaccinated with S19 or RB51). The Se of both tests was similar across Bayesian models, with values around 94%. In contrast, the Sp of the iELISA, ranging between 97 and 98%, was significantly higher than that of the cELISA, which was approximately 94–95%. The true prevalence of bB was 1.63% (95% CrI: 0.56–2.54) in non-vaccinated cattle, decreased to 0.97% (95% CrI: 0.005–2.54) in S19-vaccinated cattle and was 2.75% (95% CrI: 0.50–5.32) in RB51-vaccinated cattle. The results of this study suggest that, with similar Se and higher Sp, the iELISA based on an innovative synthetic antigen (which is more standardizable) should be recommended as a possible screening test for bB in Ecuador. Also, the proposed approach suggests insights into the quality of the vaccination campaign and highlights the need for refining the Ecuadorian national brucellosis control program. Full article

The use of lactic acid bacteria for developing functional foods is increasing for their ability to synthesize beneficial metabolites such as vitamin B (riboflavin, RF) and postbiotic compounds. Here, the spontaneous mutant FS54 B2 was isolated by treatment of the dextran-producing Weissella confusa FS54 strain with roseoflavin. FS54 B2 overproduced RF (4.9 mg/L) in synthetic medium. The FMN riboswitch is responsible for the regulation of RF biosynthesis, and sequencing of the coding DNA revealed that FS54 B2 carries the G131U mutation. FS54 B2 retained the capacity of FS54 to synthesize high levels of dextran (3.8 g/L) in synthetic medium. The fermentation capacities of the two Weissella strains was tested in commercial oat-, soy- and rice-based beverages. The best substrate for FS54 B2 was the oat-based drink, in which, after fermentation, the following were detected: RF (2.4 mg/L), dextran (5.3 mg/L), potential prebiotics (oligosaccharides (panose (5.1 g/L), isomaltose (753 mg/L) and isomaltotriose (454 mg/L)) and the antioxidant mannitol (16.3 g/L). pH-lowering ability and cell viability after one month of storage period were confirmed. As far as we know, this is the first time that an RF-overproducing W. confusa strain has been isolated, characterized and tested for its potential use in the development of functional beverages. Full article

In this study, physicochemical and proteomic analyses were performed to investigate the effect of modified atmosphere packaging (MAP) on the quality of postharvest loose-leaf lettuce. The results showed that MAP enhanced the sensory characteristics of loose-leaf lettuce and delayed the incidence of postharvest deterioration by suppressing weight loss, electrolyte leakage, and reactive oxygen species levels. MAP-inhibited storage-induced programmed cell death may be attributed to a lower expression of protein disulfide isomerase and a higher expression of oligonucleotide/oligosaccharide binding fold nucleic acid binding site protein and reducing glutamine synthase levels. Also, we explore the potential of MAP to protect against oxidative damage in loose-leaf lettuce by potentially modulating the expression levels of NAC family proteins, which may enhance signaling and the expression of cytochrome c oxidase and membrane-bound pyrophosphate in the oxidative phosphorylation pathway. In addition, MAP potentially delayed postharvest senescence and extended the shelf life of lettuce by regulating key protein metabolic pathways that may reduce respiration rates. These include the NAC family of proteins, enzymes in the oxidative phosphorylation pathway, glutamine synthetize, and other crucial metabolic routes. These findings provide a scientific basis for enhancing the postharvest preservation of leafy vegetables, such as loose-leaf lettuce, through MAP technology. Full article

Infants rely on their developing immune system and the protective components of breast milk to defend against bacterial and viral pathogens, as well as immune disorders such as food allergies, prior to the introduction of solid foods. When breastfeeding is not feasible, fortified infant formula will most frequently be offered, usually based on a cow’s milk-based substitute. The current study aimed to explore the immunomodulatory effects of combinations of commercially available human milk oligosaccharides (HMOs). An in vitro co-culture model of Caco-2 intestinal epithelial cells and THP-1 macrophages was established to replicate the hallmarks of intestinal inflammation and to evaluate the direct effects of different synthetic HMO combinations. Notably, a blend of the most prevalent fucosylated and sialylated HMOs, 2′-fucosyllactose (2′-FL) and 6′-siallylactose (6′-SL), respectively, resulted in decreased pro-inflammatory cytokine levels. These effects were dependent on the HMO concentration and on the HMO ratio resembling those in breastmilk. Interestingly, adding additional HMO structures did not enhance the anti-inflammatory effects. This research highlights the importance of carefully selecting HMO combinations in nutritional products, particularly for infant milk formulations, to effectively mimic the benefits associated with breastmilk. Full article

Most chemotherapeutic agents are poorly soluble in water, have low selectivity, and cannot reach the tumor in the desired therapeutic concentration. On the other hand, sensitive hydrophilic therapeutics like nucleic acids and proteins suffer from poor bioavailability and cell internalization. To solve this problem, new types of controlled release systems based on nano-sized self-assemblies of cyclodextrins able to control the speed, timing, and location of therapeutic release are being developed. Cyclodextrins are macrocyclic oligosaccharides characterized by a high synthetic plasticity and potential for derivatization. Introduction of new hydrophobic and/or hydrophilic domains and/or formation of nano-assemblies with therapeutic load extends the use of CDs beyond the tried-and-tested CD-drug host–guest inclusion complexes. The recent advances in nano drug delivery have indicated the benefits of the hybrid amphiphilic CD nanosystems over individual CD and polymer components. This review provides a comprehensive overview of the most recent advances in the design of CDs self-assemblies and their use for delivery of a wide range of therapeutic molecules. It aims to offer a valuable insight into the many roles of CDs within this class of drug nanocarriers as well as current challenges and future perspectives. Full article

Brucellosis in animals is an infectious disease caused by bacteria of the genus Brucella. Known methods for diagnosing brucellosis face some challenges, due to the difficulties in isolating and standardizing the natural brucellosis antigen. In this work, we investigated the possibility of using the fluorescence polarization assay (FPA) with synthetic glycoconjugate biosensing tracers to detect antibodies against Brucella as a new methodology for diagnosing brucellosis. Based on the received results, the synthetic fluorescein-labeled trisaccharide tracer is most effective for Brucellosis detection. This tracer is structurally related to the immune determinant fragment of the Brucella LPS buildup of N-formyl-d-perosamine units, connected via α-(1→3)-linkage at the non-reducing end and α-(1→2)-linkage at the reducing end. The sensitivity and specificity in the case of the use of trisaccharide tracer 3b were 71% and 100% (Yuden’s method) and 87% and 88% (Euclidean method), respectively, which is comparable with the diagnostic efficiency of traditionally used serological methods, such as the agglutination test (AT), complement fixation test (CFT), and Rose Bengal test (RBT). Given the known advantages of FPA (e.g., speed, compactness of the equipment, and standard reagents) and the increased specificity of the developed test system, it would be appropriate to consider its widespread use for the diagnosis of brucellosis in animals, including rapid testing in the field. Full article