Sugar Moiety Research Articles

New anti-pulmonary fibrosis prenylflavonoid glycosides from Epimedium koreanum.

Four new prenylflavonoid glycosides, namely koreanoside H-K (1-4), together with eleven known ones (5-15) were isolated from the leaves of Epimedium koreanum Nakai. Their structures were elucidated by 1D NMR, 2D NMR, HR-ESI-MS, IR and UV. The identification of the sugar moieties was carried out by means of acid hydrolysis and HPLC analysis of their derivatives. It is worth noting that compound 3 and compound 4 were elucidated to contain fucose and quinovose moieties, which were two extremely rare sugar units from the genus Epimedium. The anti-pulmonary fibrosis activity of the new compounds was evaluated using A549 cell line. Compounds 1, 2 and 4 showed significant anti-pulmonary fibrosis activities.

Synthesis and Biological Evaluation of novel R1, R2 substituted 2-(4-((2-(4-alkoxyphenyl)-5-methyloxazol-4-yl)methyl)-1-alkyl-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol having Anti Diabetic activity

The synthesis and biological evaluation of novel pyrazole based heterocycles attached to sugar moiety lead to creating a new molecular frame work. Nine new compounds were synthesized by reacting ethyl 2-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl) methyl)-3-oxobutanoate derivatives (9a-9c) with different alkyl hydrazines to give various substituted 4-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl) methyl)-5-methyl-1H-pyrazol-3-ol derivatives (10 a-10i) which in turn were reacted with bromoglucose (3)to yield R1, R2 substituted 2-(4-((2-(4-alkoxyphenyl)-5-methyloxazol-4-yl)methyl)-1-alkyl-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (12a-12i). The chemical structures of the synthesized compounds were characterized by means of IR, Mass and NMR spectroscopy. The compounds were screened for anti-diabetic activity by urinary glucose excretion method (UGE). Among the compounds tested, 12f, 12h and12i have exhibited moderate anti-diabetic activity as that of standard drug, remogliflozin. These compounds can be further exploited to get the potent lead compound.

The stem rust effector protein AvrSr50 escapes Sr50 recognition by a substitution in a single surface-exposed residue.

Summary Pathogen effectors are crucial players during plant colonisation and infection. Plant resistance mostly relies on effector recognition to activate defence responses. Understanding how effector proteins escape from plant surveillance is important for plant breeding and resistance deployment.Here we examined the role of genetic diversity of the stem rust (Puccinia graminis f. sp. tritici (Pgt)) AvrSr50 gene in determining recognition by the corresponding wheat Sr50 resistance gene. We solved the crystal structure of a natural variant of AvrSr50 and used site‐directed mutagenesis and transient expression assays to dissect the molecular mechanisms explaining gain of virulence.We report that AvrSr50 can escape recognition by Sr50 through different mechanisms including DNA insertion, stop codon loss or by amino‐acid variation involving a single substitution of the AvrSr50 surface‐exposed residue Q121. We also report structural homology of AvrSr50 to cupin superfamily members and carbohydrate‐binding modules indicating a potential role in binding sugar moieties.This study identifies key polymorphic sites present in AvrSr50 alleles from natural stem rust populations that play important roles to escape from Sr50 recognition. This constitutes an important step to better understand Pgt effector evolution and to monitor AvrSr50 variants in natural rust populations.

Synthesis, Characterization and Molecular Docking of New Nucleosides and Schiff Bases Derived from Ampyrone as Antiviral Agents to Contain the COVID-19 Virus

A new series of nucleoside derivatives was prepared from the reaction of 4-aminoantipyrene with different sugar moieties. In addition, ampyrone’s reaction with different aromatic aldehydes gave the corresponding Schiff base derivatives, which were also synthesized. Both molecular docking and in vitro antiviral activities at different concentrations of different synthesized compounds against SARS-CoV-2 were screened. All newly synthesized compounds were characterized on the basis of IR, 1H NMR and 13C NMR spectral data and physical data. The compounds were screened for potential cytotoxic activities. The molecular docking analysis showed that compounds 6b, 6e, 6c, 6f and 6d exhibited relatively higher binding energies (−8.1, −8.1, −8.3, −8.4 and −8.7 kcal/mol, respectively) compared to all the other compounds. However, the different compounds did not show any promising in vitro antiviral activities against SARS-CoV-2.

Convenient and General Synthesis of C-3-Substituted Het(aryl)indole C-Nucleoside Analogues from Sugar Alkynes

AbstractThe synthesis of C-3-substituted het(aryl)indole C-nucleoside analogues bearing structurally diverse sugar moieties has been achieved by Sonogashira coupling of terminal sugar alkynes with het(aryl) iodides followed by heteroannulation of the corresponding sugar/het(aryl) alkynes with substituted 2-iodoanilines. This method is simple and general and is suitable for structurally diverse sugars and various het(aryl) iodides. The terminal sugar alkynes include furanosides, pyranosides, and acyclic sugars with sensitive groups and bulky substituents. The het(aryl) iodides involve iodobenzene, iodothiophene, iodobenzothiophene, and iodobenzofuran. Thirty-one examples are presented and the corresponding 2-het(aryl)indole C-nucleoside analogues are obtained in moderate to excellent yields.

Microbial Bioconversion of Phenolic Compounds in Agro-industrial Wastes: A Review of Mechanisms and Effective Factors.

Agro-industrial wastes have gained great attention as a possible source of bioactive compounds, which may be utilized in various industries including pharmaceutics, cosmetics, and food. The food processing industry creates a vast amount of waste which contains valuable compounds such as phenolics. Polyphenols can be found in soluble (extractable or free), conjugated, and insoluble-bound forms in various plant-based foods including fruits, vegetables, grains, nuts, and legumes. A substantial portion of phenolic compounds in agro-industrial wastes is present in the insoluble-bound form attached to the cell wall structural components and conjugated form which is covalently bound to sugar moieties. These bound phenolic compounds can be released from wastes by hydrolysis of the cell wall and glycosides by microbial enzymes. In addition, they can be converted into unique metabolites by methylation, carboxylation, sulfate conjugation, hydroxylation, and oxidation ability of microorganisms during fermentation. Enhancement of concentration and antioxidant activity of phenolic compounds and production of new metabolites from food wastes by microbial fermentation might be a promising way for better utilization of natural resources. This review provides an overview of mechanisms and factors affecting release and bioconversion of phenolic compounds in agro-industrial wastes by microbial fermentation.

A Molecular Investigation of the Solvent Influence on Inter- and Intra-Molecular Hydrogen Bond Interaction of Linamarin

Linamarin has been reported to have anticancer activities; however, its extraction and isolation using different solvents yield a low amount. Therefore, understanding the physical properties, such as solvents’ solubility, membrane permeability and lipophilicity and how they are associated with different solvents, is a paramount topic for discussion, especially for its potential as a drug. Linamarin has a sugar moiety with many polar groups responsible for its physical properties. Following current trends, a molecular dynamics simulation is performed to investigate its physical properties and how different solvents, such as water, methanol (MeOH), dimethyl sulfoxide (DMSO) and dichloromethane (DCM), affect such properties. In this work, we have investigated the influence of intermolecular and intramolecular hydrogen bonding and the influence of polar and non-polar solvents on the physical properties of linamarin. Furthermore, solvation free-energy and electronic structure analysis are performed. The structural analysis results show that the polar groups of linamarin have strong interactions with all solvents except the etheric oxygen groups. A detailed analysis shows intermolecular hydrogen bonding between polar solvents (water, MeOH and DMSO) and the hydroxyl oxygens of linamarin. Water exhibits the strongest interaction with linamarin’s functional groups among the investigated solvents. The findings show that within the first solvation shell, the number of water molecules is greatest, while MeOH has the fewest. Centrally to the structural analysis, solvation free energy confirms DMSO to be the best solvent since it prefers to interact with linamarin over itself, while water prefers to interact with itself. While the solute–solvent interactions are strongest between linamarin and water, the solvent–solvent interactions are strongest in water. As a result, the solvation free-energy calculations reveal that linamarin solvation is most favourable in DMSO.

De Novo Biosynthesis of Oleanane-Type Ginsenosides in Saccharomyces cerevisiae Using Two Types of Glycosyltransferases from Panax ginseng

Oleanane-type ginsenosides are highly biologically active substances in Panax ginseng, a popular Chinese dietary plant. Lack of key enzymes for glycosylation reactions has hindered de novo synthesis of these bioactive molecules. We mined candidate glycosyltransferases (GTs) of the ginseng database by combining key metabolites and transcriptome coexpression analyses and verified their function using in vitro enzymatic assays. The PgCSyGT1, a cellulose synthase-like GT rather than a UDP-dependent glucuronosyltransferase (UGT), was verified as the key enzyme for transferring a glucuronosyl moiety to the free C3-OH of oleanolic acid to synthesize calenduloside E. Two UGTs (PgUGT18 and PgUGT8) were first identified as, respectively, catalyzing the glycosylation reaction of the second sugar moiety of C3 and the C28 in the oleanane-type ginsenoside biosynthetic pathway. Then, we integrated these GTs in combinations into Saccharomyces cerevisiae genome and realized de novo biosynthesis of oleanane-type ginsenosides with a yield of 1.41 μg/L ginsenoside Ro in shake flasks. This report provides a basis for effective biosynthesis of diverse oleanane-type ginsenosides in microbial cell factories.

Leucine-Rich, Potent Anti-Bacterial Protein against Vibrio cholerae, Staphylococcus aureus from Solanum trilobatum Leaves.

A 24 kDa leucine-rich protein from ion exchange fractions of Solanum trilobatum, which has anti-bacterial activity against both the Gram-negative Vibrio cholerae and Gram-positive Staphylococcus aureus bacteria has been purified. In this study, mass spectrometry analysis identified the leucine richness and found a luminal binding protein (LBP). Circular dichroism suggests that the protein was predominantly composed of α- helical contents of its secondary structure. Scanning electron microscopy visualized the characteristics and morphological and structural changes in LBP-treated bacterium. Further in vitro studies confirmed that mannose-, trehalose- and raffinose-treated LBP completely inhibited the hemagglutination ability towards rat red blood cells. Altogether, these studies suggest that LBP could bind to sugar moieties which are abundantly distributed on bacterial surface which are essential for maintaining the structural integrity of bacteria. Considering that Solanum triolbatum is a well-known medicinal and edible plant, in order to shed light on its ancient usage in this work, an efficient anti-microbial protein was isolated, characterized and its in vitro functional study against human pathogenic bacteria was evaluated.

Steroidal alkaloids and their glycosides from the bulbs of Fritillaria unibracteata

Seven undescribed steroidal alkaloids, including two jervine-type steroidal alkaloids, fritiunibras A-B (1–2), and five cevanine-type steroidal alkaloid glycosides, fritiunibras C-G (3–7), along with six known cevanine-type steroidal alkaloids and their glycosides (8–13) were isolated from the bulbs of Fritillaria unibracteata Hsiao et K. C. Hsia. Their structures were determined by interpretation of comprehensive spectroscopic and single-crystal X-ray diffraction analysis. The absolute configurations of sugar moieties were determined by HPLC analysis and compared with standards after hydrolysis and derivatization. Furthermore, their inhibitory effects on NO production and cytotoxic activities were evaluated.

Nucleic Acids and Their Analogues for Biomedical Applications.

Nucleic acids are emerging as powerful and functional biomaterials due to their molecular recognition ability, programmability, and ease of synthesis and chemical modification. Various types of nucleic acids have been used as gene regulation tools or therapeutic agents for the treatment of human diseases with genetic disorders. Nucleic acids can also be used to develop sensing platforms for detecting ions, small molecules, proteins, and cells. Their performance can be improved through integration with other organic or inorganic nanomaterials. To further enhance their biological properties, various chemically modified nucleic acid analogues can be generated by modifying their phosphodiester backbone, sugar moiety, nucleobase, or combined sites. Alternatively, using nucleic acids as building blocks for self-assembly of highly ordered nanostructures would enhance their biological stability and cellular uptake efficiency. In this review, we will focus on the development and biomedical applications of structural and functional natural nucleic acids, as well as the chemically modified nucleic acid analogues over the past ten years. The recent progress in the development of functional nanomaterials based on self-assembled DNA-based platforms for gene regulation, biosensing, drug delivery, and therapy will also be presented. We will then summarize with a discussion on the advanced development of nucleic acid research, highlight some of the challenges faced and propose suggestions for further improvement.

Unlocking the Hydrolytic Mechanism of GH92 α-1,2-Mannosidases: Computation Inspires the use of C-Glycosides as Michaelis Complex Mimics.

The conformational changes in a sugar moiety along the hydrolytic pathway are key to understand the mechanism of glycoside hydrolases (GHs) and to design new inhibitors. The two predominant itineraries for mannosidases go via O S 2→B 2,5→1 S 5 and 3 S1 →3 H 4→1 C 4. For the CAZy family 92, the conformational itinerary was unknown. Published complexes of Bacteroides thetaiotaomicron GH92 catalyst with a S‐glycoside and mannoimidazole indicate a 4 C 1→4 H 5/1 S 5→1 S 5 mechanism. However, as observed with the GH125 family, S‐glycosides may not act always as good mimics of GH's natural substrate. Here we present a cooperative study between computations and experiments where our results predict the E 5→B 2,5/1 S 5→1 S 5 pathway for GH92 enzymes. Furthermore, we demonstrate the Michaelis complex mimicry of a new kind of C‐disaccharides, whose biochemical applicability was still a chimera.

Iridoid glucosides from the leaves of Vitex negundo var. cannabifolia

• Five new and nine known iridoid glucosides were obtained from the leaves of Vitex negundo var. cannabifolia . • The absolute configurations of sugar moieties were determined using a HPLC-UV-based method. • Six isolates increased the cell viability of GES-1 cell insulted by TCA. Five new iridoid glucosides, cannabifolisides A–E ( 1 – 5 ), together with nine analogues ( 6 – 14 ), were isolated from the leaves of Vitex negundo var. cannabifolia. Their structures were elucidated by spectroscopic data (NMR, UV, IR, and MS) analyses and comparison of their spectroscopic and physical data with the literature values. The protective effect of isolated compounds on human gastric epithelial cells were evaluated by measuring the enhanced cell viability of GES-1 cell insulted by TCA. Among these, compounds 4 , 6 , 8 , 10 , 12 , and 14 remarkably increased the cell viability in a concentration-depend manner.

Identification of 20(S)-Ginsenoside Rh2 as a Potential EGFR Tyrosine Kinase Inhibitor.

As the main active ingredients of Panax ginseng, ginsenosides possess numerous bioactivities. Epidermal growth factor receptor (EGFR) was widely used as a valid target in anticancer therapy. Herein, the EGFR targeting activities of 20(S)-ginsenoside Rh2 (20(S)-Rh2) and the relationship of their structure-activity were investigated. Homogeneous time-resolved fluorescence assay showed that 20(S)-Rh2 significantly inhibited the activity against EGFR kinase. 20(S)-Rh2 was confirmed to effectively inhibited cell proliferation in a dose-dependent manner by MTT assay. Furthermore, quantitative real-time PCR and western blotting analysis revealed that 20(S)-Rh2 inhibited A549 cells growth via the EGFR-MAPK pathway. Meanwhile, 20(S)-Rh2 could promote cell apoptosis, block cell cycle, and reduce cell migration of A549 cells, respectively. In silico, the result suggested that both hydrophobic interactions and hydrogen-bonding interactions could contribute to stabilize their binding. Molecular dynamics simulation showed that the side chain sugar moiety of 20(S)-Rh2 was too flexible to be fixed at the active site of EGFR. Collectively, these findings suggested that 20(S)-Rh2 might serve as a potential EGFR tyrosine kinase inhibitor.

Magnesium rescues the morphology of Bacillus subtilis mreB mutants through its inhibitory effect on peptidoglycan hydrolases

Cell wall homeostasis in bacteria is tightly regulated by balanced synthesis and degradation of peptidoglycan (PG), allowing cells to expand their sacculus during growth while maintaining physical integrity. In rod-shaped bacteria, actin-like MreB proteins are key players of the PG elongation machinery known as the Rod complex. In the Gram-positive model bacterium Bacillus subtilis depletion of the essential MreB leads to loss of rod shape and cell lysis. However, millimolar concentrations of magnesium in the growth medium rescue the viability and morphological defects of mreB mutants by an unknown mechanism. Here, we used a combination of cytological, biochemical and biophysical approaches to investigate the cell surface properties of mreB null mutant cells and the interactions of Mg2+ with the cell wall of B. subtilis. We show that ∆mreB cells have rougher and softer surfaces, and changes in PG composition indicative of increased DL- and DD-endopeptidase activities as well as increased deacetylation of the sugar moieties. Increase in DL-endopeptidase activity is mitigated by excess Mg2+ while DD-endopeptidase activity remains high. Visualization of PG degradation in pulse-chase experiments showed anisotropic PG hydrolase activity along the sidewalls of ∆mreB cells, in particular at the sites of increased cell width and bulging, while PG synthesis remained isotropic. Overall, our data support a model in which divalent cations maintain rod shape in ∆mreB cells by inhibiting PG hydrolases, possibly through the formation of crosslinks with carboxyl groups of the PG meshwork that affect the capacity of PG hydrolases to act on their substrate.

Three Novel Bacteriophages, J5a, F16Ba, and z1a, Specific for Bacillus anthracis, Define a New Clade of Historical Wbeta Phage Relatives.

Bacillus anthracis is a potent biowarfare agent, able to be highly lethal. The bacteria dwell in the soil of certain regions, as natural flora. Bacteriophages or their lytic enzymes, endolysins, may be an alternative for antibiotics and other antibacterials to fight this pathogen in infections and to minimize environmental contamination with anthrax endospores. Upon screening environmental samples from various regions in Poland, we isolated three new siphophages, J5a, F16Ba, and z1a, specific for B. anthracis. They represent new species related to historical anthrax phages Gamma, Cherry, and Fah, and to phage Wbeta of Wbetavirus genus. We show that the new phages and their closest relatives, phages Tavor_SA, Negev_SA, and Carmel_SA, form a separate clade of the Wbetavirus genus, designated as J5a clade. The most distinctive feature of J5a clade phages is their cell lysis module. While in the historical phages it encodes a canonical endolysin and a class III holin, in J5a clade phages it encodes an endolysin with a signal peptide and two putative holins. We present the basic characteristic of the isolated phages. Their comparative genomic analysis indicates that they encode two receptor-binding proteins, of which one may bind a sugar moiety of B. anthracis cell surface.

Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution.

Sugars are crucial components in biosystems and industrial applications. In aqueous environments, the natural state of short saccharides or charged glycosaminoglycans is floating and wiggling in solution. Therefore, tools to characterize their structure in a native aqueous environment are crucial but not always available. Here, we show that a combination of Raman/ROA and, on occasions, NMR experiments with Molecular Dynamics (MD) and Quantum Mechanics (QM) is a viable method to gain insights into structural features of sugars in solutions. Combining these methods provides information about accessible ring puckering conformers and their proportions. It also provides information about the conformation of the linkage between the sugar monomers, i.e., glycosidic bonds, allowing for identifying significantly accessible conformers and their relative abundance. For mixtures of sugar moieties, this method enables the deconvolution of the Raman/ROA spectra to find the actual amounts of its molecular constituents, serving as an effective analytical technique. For example, it allows calculating anomeric ratios for reducing sugars and analyzing more complex sugar mixtures to elucidate their real content. Altogether, we show that combining Raman/ROA spectroscopies with simulations is a versatile method applicable to saccharides. It allows for accessing many features with precision comparable to other methods routinely used for this task, making it a viable alternative. Furthermore, we prove that the proposed technique can scale up by studying the complicated raffinose trisaccharide, and therefore, we expect its wide adoption to characterize sugar structural features in solution.

Sweet Boron: Boron-Containing Sugar Derivatives as Potential Agents for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is a binary type of radiotherapy for the treatment of cancer. Due to recent developments of neutron accelerators and their installation in some hospitals, BNCT is on the rise worldwide and is expected to have a significant impact on patient treatments. Therefore, there is an increasing need for improved boron delivery agents. Among the many small molecules and delivery systems developed, a significant amount of recent research focused on the synthesis of boron-containing sugar and amino acid derivatives to exploit specific transport proteins, as d-glucose transporter 1 (GLUT1) and large neutral amino acid transporter (LAT1), overexpressed by tumor cells. This review will discuss the last year’s achievements in the synthesis and some biological evaluation of boronated sugars derivatives. The compounds described in this review are intrinsically asymmetric due to the presence of chiral sugar moieties, often joined to boron clusters, which are structural elements with high symmetry.

Synthesis and antiviral activity of formycin derivatives with anti-influenza virus activity

In a screening using our unique natural product library, the C-nucleoside antibiotic formycin A, which exerts strong anti-influenza virus activity, was rediscovered. Aiming to develop a new type of anti-influenza virus drug, we synthesized new derivatives of formycin and evaluated its anti-influenza virus activity. Structural modifications were focused on the base moiety and sugar portion, respectively, and >40 novel formycin derivatives were synthesized. Modification of the C-7 position of the pyrazolopyrimidine ring strongly contributed to improve the activity. In particular, excellent anti-influenza virus activity was observed in the NHMe (10), SMe (12), and SeMe (15) derivatives, in which heteroatoms were introduced. In addition, in the modification of the sugar moiety, the presence of a hydroxyl group and its stereochemistry greatly affected both the expression and intensity of the activity. Furthermore, the evaluation results of the 7-SEt derivative (29) and the 2′-modified derivative (59) suggested that structural modifications may reduce cytotoxicity.

The modulation of cAMP/PKA pathway by asiaticoside ameliorates high glucose-induced inflammation and apoptosis of retinal pigment epithelial cells.

Asiaticoside, the major bioactive constituent purified from Centella asiatica, is a pentacyclic triterpene saponin with sugar moieties (glucose-glucose-rhamnose). Its biological activities including anti-inflammation and antioxidant have been widely reported. This study aimed to investigate the role of asiaticoside in diabetic retinopathy (DR). Human retinal pigment epithelium (RPE) cells ARPE-19 were induced by high glucose. Then, cell survival rate, expression of inflammatory factors, oxidative stress, and apoptosis were measured by MTT method, western blot, oxidative stress detection kits and TUNEL respectively. To uncover the underlying mechanism, the levels of cyclic AMP (cAMP) and protein kinase A (PKA) were measured by Enzyme linked immunosorbent assay (ELISA) and PKA activities were detected by the Kemptide phosphorylation assay. Furthermore, cAMP inhibitor SQ22536 was also used to validate the mechanism. Asiaticoside suppressed the inflammation and apoptosis of ARPE-19 cells, and the activities of cAMP and PKA were inhibited upon HG induction while again released after further administration of asiaticoside. However, these effects were all abolished by SQ22536. In conclusion, we have demonstrated in this paper that asiaticoside ameliorates high glucose-induced inflammation and apoptosis of RPE cells by activating cAMP/PKA signaling pathway. asiaticoside-mediated activation of cAMP/PKA signaling pathway may serve as a potential target for the management of DR.