Glycosylation Of Compounds Research Articles

Photocatalytic Synthesis of α-Ketonyl Glycosyl Compounds from Glycosyl Thiols and Silyl Enol Ethers.

The synthesis of C1-ketonyl glycosyl compounds featuring α-selectivity has seldom been reported. We herein devise a glycosyl radical-based approach to facilely access stereoenriched ketonyl glycosyl compounds via an Ir photoredox-catalyzed desulfurative addition to silyl enol ethers, using in situ-generated tetrafluoropyridinyl thioglycosides from glycosyl 1-thiols as radical precursors. This protocol features readily prepared starting materials, mild conditions, excellent functional group tolerance, satisfactory scale-up, and notable amenability to late-stage modification of pharmaceutically relevant complex molecules.

Direct radical functionalization of native sugars

Naturally occurring (native) sugars and carbohydrates contain numerous hydroxyl groups of similar reactivity1,2. Chemists, therefore, rely typically on laborious, multi-step protecting-group strategies3 to convert these renewable feedstocks into reagents (glycosyl donors) to make glycans. The direct transformation of native sugars to complex saccharides remains a notable challenge. Here we describe a photoinduced approach to achieve site- and stereoselective chemical glycosylation from widely available native sugar building blocks, which through homolytic (one-electron) chemistry bypasses unnecessary hydroxyl group masking and manipulation. This process is reminiscent of nature in its regiocontrolled generation of a transient glycosyl donor, followed by radical-based cross-coupling with electrophiles on activation with light. Through selective anomeric functionalization of mono- and oligosaccharides, this protecting-group-free ‘cap and glycosylate’ approach offers straightforward access to a wide array of metabolically robust glycosyl compounds. Owing to its biocompatibility, the method was extended to the direct post-translational glycosylation of proteins.

Biocontrol fungi induced stem-base rot disease resistance of Morinda officinalis How revealed by transcriptome analysis.

Morinda officinalis How (MO) is a Rubiaceae plant, and its medicinal part is dried root, which is one of the "Four Southern Medicines" in China. At present, the plant MO breed seedlings mainly by cutting methods. Long-term asexual propagation makes pathogenic fungi accumulate in MO, leading to stem-base rot, which is caused by Fusarium oxysporum (Fon). In this study, we used Trichoderma harzianum and Pestalotiopsis sp. as biocontrol fungi to investigate their antagonistic ability to Fon through in vitro antagonism and pot experiments, and combined with transcriptome sequencing to explore the mechanism of biocontrol. The results showed that both Trichoderma harzianum and Pestalotiopsis sp. could inhibit the growth of Fon. In addition, Trichoderma harzianum and Pestalotiopsis sp. could also enhance the basic immunity to Fon by increasing the activities of defensive enzymes such as POD and SOD, chlorophyll content, soluble sugar content, and oligosaccharide content of MO. The mechanism of biological control of stem-base rot of MO was discussed by transcriptome technology. MO was treated with two treatments, root irrigation with biocontrol fungi or inoculation with Fon after root irrigation with biocontrol fungi. Transcriptome sequencing revealed that nearly 11,188 differentially expressed genes (DEGs) were involved in the process of inducing MO systemic resistance to Fon by biocontrol fungi. Meanwhile, Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, as well as transcription factor (TFs) prediction showed that there were significant differences in the expression levels of MO roots under different treatments. Also, the genes of the "MAPK signaling pathway" and "plant hormone signaling pathway" were analyzed, in which the ERFs gene of the ethylene signal transduction pathway participated in the metabolism of glycosyl compounds. It is speculated that the ethylene signal may participate in the immune response of the sugar signal to the infection of Fon. After qRT-PCR verification of 10 DEGs related to the ethylene signal transduction pathway, the expression trend is consistent with the results of transcriptome sequencing, which proves the reliability of transcriptome sequencing. In conclusion, this study preliminarily identified the molecular mechanism of the biological control of MO stem-base rot and provided a scientific basis for further research on the prevention and control mechanism of MO stem-base rot.

Research progress and application of enzymatic synthesis of glycosyl compounds

Research progress and application of enzymatic synthesis of glycosyl compounds

Diversification of Glycosyl Compounds via Glycosyl Radicals.

Glycosyl radical functionalization is one of the central topics in synthetic carbohydrate chemistry. Recent advances in metal-catalyzed cross-coupling chemistry and metallaphotoredox catalysis provided powerful platforms for glycosyl radical diversification. In particular, the discovery of new glycosyl radical precursors in conjunction with these advanced reaction technologies have significantly expanded the space for glycosyl compound synthesis. In this Minireview, we highlight the most recent progress in this area starting from 2021, and the reports included will be categorized based on different reaction types for better clarity.

Diversification of Glycosyl Compounds via Glycosyl Radicals

AbstractGlycosyl radical functionalization is one of the central topics in synthetic carbohydrate chemistry. Recent advances in metal‐catalyzed cross‐coupling chemistry and metallaphotoredox catalysis provided powerful platforms for glycosyl radical diversification. In particular, the discovery of new glycosyl radical precursors in conjunction with these advanced reaction technologies have significantly expanded the space for glycosyl compound synthesis. In this Review, we highlight the most recent progress in this area starting from 2021, and the reports included will be categorized based on different reaction types for better clarity.

Modular Click Assembly DNA-Encoded Glycoconjugate Libraries with on-DNA Functional Group Transformations.

Carbohydrates are an important class of naturally active products and play vital roles in regulating various physiological activities. To meet the demand for carbohydrate-based libraries used for the identification of potential drug candidates for pharmaceutical-related targets, we developed a set of on-DNA protocols to construct the DNA-encoded glycoconjugates, including Seyferth-Gilbert homologation, anomeric azidation, and CuAAC cyclization. These on-DNA chemistries enable the generation and modification of DNA-linked glycosyl compounds with good conversions and broad substrate scope. Finally, three DNA-linked glycoconjugate libraries were successfully generated to demonstrate their applicability and feasibility in library preparation.

Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains.

Nonalcoholic fatty liver disease (NAFLD) encompasses nonalcoholic steatohepatitis (NASH) and affects 25% of the global population. Although a plethora of experimental models for studying NASH have been proposed, still scarce findings regarding the hepatic metabolomic/molecular profile. In the present study, we sought to unravel the hepatic metabolomic profile of mice subjected to a hybrid model of NASH, by combining a Western diet and carbon tetrachloride administration, for 8 weeks, in male C57BL/6J and BALB/c mice. In both mouse strains, the main traits of NASH-metabolic (glucose intolerance profile), morphologic (extensive microvesicular steatosis and fibrosis, lobular inflammation, and adipose tissue-related inflammation/hypertrophy), and molecular (impaired Nrf2/NF-κB pathway dynamics and altered metabolomic profile)-were observed. The hepatic metabolomic profile revealed that the hybrid protocol impaired, in both strains, the abundance of branched chain-aromatic amino acids, carboxylic acids, and glycosyl compounds, that might be linked to the Nrf2 pathway activation. Moreover, we observed a strain-dependent hepatic metabolomic signature, in which the tricarboxylic acid metabolites and pyruvate metabolism were dissimilarly modulated in C57BL/6J and BALB/c mice. Thus, we provide evidence that the strain-dependent hepatic metabolomic profile might be linked to the distinct underlying mechanisms of NASH, also prospecting potential mechanistic insights into the corresponding disease.

Untargeted metabolism approach reveals difference of varieties of bud and relation among characteristics of grafting seedlings in Camellia oleifera.

Camellia oleifera is one of the essential wood oil trees in the world. C.oleifera was propagated by nurse seedling grafting. Since the scion of C.oleifera had a significant regulated effect on the properties of rootstock after grafting and impacted on the growth of the grafted seedlings, it was necessary to understand the characteristics of buds among varieties to cultivate high-quality grafted seedlings. The metabolome was thought to be a powerful tool for understanding connecting phenotype-genotype interactions, which has an important impact on plant growth and development. In this study, UPLC-MS was used to determine the metabolites of the apical buds of CL3, CL4, CL40, and CL53 spring shoots after 30 days of sprout and to measure the growth characteristics of roots and stems after grafting. Metabolomics analysis revealed 554 kinds of metabolites were significant differences among four varieties, and 29 metabolic pathways were identified to have significant changes (p< 0.05), including carboxylic acids and derivatives, fatty Acyls, organooxygen compounds, and prenol lipids metabolites. The metabolites appeared in all varieties, including phenethyl rutinoside in glycosyl compounds and hovenidulcioside A1 in terpene glycosides. Metabolite-metabolite correlations in varieties revealed more complex patterns in relation to bud and enabled the recognition of key metabolites (e.g., Glutamate, (±)Catechin, GA52, ABA, and cs-Zeatin) affecting grafting and growth ability. Each variety has a unique metabolite type and correlation network relationship. Differentiated metabolites showed different growth trends for development after grafting. Many metabolites regulate the growth of scions in buds before grafting, which plays a crucial role in the growth of seedlings after grafting. It not only regulates the growth of roots but also affects the development of this stem. Finally, those results were associated with the genetic background of each cultivar, showing that metabolites could be potentially used as indicators for the genetic background, indicating that metabolites could potentially be used as indicators for seedling growth characteristics. Together, this study will enrich the theoretical basis of seedling growth and lay a foundation for further research on the molecular regulation mechanism interaction between rootstock and scion, rootstock growth, and the development of grafted seedlings after grafting.

Single-component hyaluronic acid hydrogel adhesive based on phenylboronic ester bonds for hemostasis and wound closure

Hydrogel tissue adhesives that currently available are often fabricated by mixing two or more polymeric components. Single-component hydrogels afford injectability, strong and reversible adhesion remain a formidable challenge. This research describes the creation of the first single-component hyaluronic acid hydrogel adhesive-based on phenylboronic acid-diol ester linkages. Phenylboronic acid can not only serve as a cross-linker to form hydrogel, but also act as an adhesion site for glycosyl compounds found in biological cell membranes. The rheological and compressive tests for the hydrogel show that it has excellent self-healing properties, good injectability and strong compressive strength. Adhesion tests demonstrated that the hydrogel has significantly greater adhesion strength than commercial fibrin glue. These findings suggest that the rational design of hydrogel precursors facilitates the formation of single-component networks and multiple functionalities. In vivo studies further proved the hydrogel was an ideal bio-adhesive with biocompatibility, absorbed wound exudate and hemostasis, and accelerated wound closure.

Integrating untargeted metabolites and targeted analysis for discrimination of kiwifruits from different cultivars

To investigate the differences among kiwifruits from six different cultivars (Actinidia chinensis, Actinidia delicosa and Actinidia arguta), UPLC-QTOF-MS and UPLC-ESI-MS/MS coupled to multivariate statistical analysis were applied to untargeted metabolites and targeted analysis of kiwifruit samples for the first time. In untargeted analysis, the metabolome of kiwifruits was exhibited by principal component analysis (PCA), a total of 44 up-regulated feature compounds were screened based on the orthogonal partial least squares-discriminant analysis (OPLS-DA) and identified as glycosyl compounds, hydrocinnamic acids and various flavonoids. Furthermore, the contents of 27 targeted procyanidins, flavonoids and hydrocinnamic acids were analyzed by a UPLC-ESI-MS/MS method. It was indicated that phenol glycosides were much higher in A. arguta, responsible for the aroma of kiwifruits, various quercetin glycosides were higher in A. arguta, and much higher flavan-3-ols and hydrocinnamic acids were rich in A. Chinensis cv. Hongyang (red) kiwifruits. In addition, the results of chemometric analysis showed the untargeted metabolites and targeted compounds were responsible for the classification on the kiwifruits, which can benefit the scientific understanding of chemical diversity for kiwifruits, and improve the investigation of new wild kiwifruit cultivars, especially red kiwifruit and A. arguta.

Diastereoselective Synthesis of Aryl C-Glycosides from Glycosyl Esters via C-O Bond Homolysis.

C-aryl glycosyl compounds offer better in vivo stability relative to O- and N-glycoside analogues. C-aryl glycosides are extensively investigated as drug candidates and applied to chemical biology studies. Previously, C-aryl glycosides were derived from lactones, glycals, glycosyl stannanes, and halides, via methods displaying various limitations with respect to the scope, functional-group compatibility, and practicality. Challenges remain in the synthesis of C-aryl nucleosides and 2-deoxysugars from easily accessible carbohydrate precursors. Herein, we report a cross-coupling method to prepare C-aryl and heteroaryl glycosides, including nucleosides and 2-deoxysugars, from glycosyl esters and bromoarenes. Activation of the carbohydrate substrates leverages dihydropyridine (DHP) as an activating group followed by decarboxylation to generate a glycosyl radical via C-O bond homolysis. This strategy represents a new means to activate alcohols as a cross-coupling partner. The convenient preparation of glycosyl esters and their stability exemplifies the potential of this method in medicinal chemistry.

Diastereoselective Synthesis of Aryl C‐Glycosides from Glycosyl Esters via C−O Bond Homolysis

AbstractC‐aryl glycosyl compounds offer better in vivo stability relative to O‐ and N‐glycoside analogues. C‐aryl glycosides are extensively investigated as drug candidates and applied to chemical biology studies. Previously, C‐aryl glycosides were derived from lactones, glycals, glycosyl stannanes, and halides, via methods displaying various limitations with respect to the scope, functional‐group compatibility, and practicality. Challenges remain in the synthesis of C‐aryl nucleosides and 2‐deoxysugars from easily accessible carbohydrate precursors. Herein, we report a cross‐coupling method to prepare C‐aryl and heteroaryl glycosides, including nucleosides and 2‐deoxysugars, from glycosyl esters and bromoarenes. Activation of the carbohydrate substrates leverages dihydropyridine (DHP) as an activating group followed by decarboxylation to generate a glycosyl radical via C−O bond homolysis. This strategy represents a new means to activate alcohols as a cross‐coupling partner. The convenient preparation of glycosyl esters and their stability exemplifies the potential of this method in medicinal chemistry.

Study of Urinary N-Acetyl-Beta-D-Glucosaminidase as a biomarker of Diabetic Nephropathy

Background: Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients worldwide. Plenty of tubular damage biomarkers have been discovered. Urinary N-acetyl-β-D-glucosaminidase (NAG) is a hydrolytic enzyme that acts on glycosyl compounds. NAG is excreted in abnormally high amounts in many renal diseases. Objective: The aim of this work was to study the importance of Urinary N acetyl-β-D-glucosaminidase level as an early biomarker for detection of DN and to assess the degree of kidney affection in various stages of DN. Patients and methods: 100 subjects divided into five groups: Group 1: 20 healthy volunteers (control group), group 2: 20 pre diabetic persons, group 3: 20 normo-albuminuria diabetic patients, group 4: 20 micro-albuminuria diabetic patients (ACR 3 -300 mg/mmol) and group 5: 20 macro-albuminuria diabetic patients (ACR ≥ 300 mg/mmol). All individuals were subjected to full history taking, ECG & echocardiography, abdominal ultrasound, laboratory investigations (HbA1c, fasting and post prandial blood glucose, lipid profile, oral glucose tolerance test (OGTT), blood urea, serum creatinine, serum uric acid, e-GFR and urinary NAG. Results: There was high significant difference between the five groups regarding duration of the disease, fasting blood sugar, postprandial blood glucose, HbA1c, Serum cholesterol, albumin/creatinine ratio, serum urea and creatinine, e-GFR and urinary NAG. In addition, there was significant positive correlation between urinary NAG and albumin/creatinine ratio, blood urea, creatinine, and e-GFR. Conclusion: The urinary NAG can be used as an early urinary biomarker for early detection and progression of diabetic nephropathy in type 2 diabetic patients.

Study of Urinary N-Acetyl-Beta-D-Glucosaminidase as a biomarker of Diabetic Nephropathy

Background: Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients worldwide. Plenty of tubular damage biomarkers have been discovered. Urinary N-acetyl-β-D-glucosaminidase (NAG) is a hydrolytic enzyme that acts on glycosyl compounds. NAG is excreted in abnormally high amounts in many renal diseases. Objective: The aim of this work was to study the importance of Urinary N acetyl-β-D-glucosaminidase level as an early biomarker for detection of DN and to assess the degree of kidney affection in various stages of DN. Patients and methods: 100 subjects divided into five groups: Group 1: 20 healthy volunteers (control group), group 2: 20 pre diabetic persons, group 3: 20 normo-albuminuria diabetic patients, group 4: 20 micro-albuminuria diabetic patients (ACR 3 -300 mg/mmol) and group 5: 20 macro-albuminuria diabetic patients (ACR ≥ 300 mg/mmol). All individuals were subjected to full history taking, ECG & echocardiography, abdominal ultrasound, laboratory investigations (HbA1c, fasting and post prandial blood glucose, lipid profile, oral glucose tolerance test (OGTT), blood urea, serum creatinine, serum uric acid, e-GFR and urinary NAG. Results: There was high significant difference between the five groups regarding duration of the disease, fasting blood sugar, postprandial blood glucose, HbA1c, Serum cholesterol, albumin/creatinine ratio, serum urea and creatinine, e-GFR and urinary NAG. In addition, there was significant positive correlation between urinary NAG and albumin/creatinine ratio, blood urea, creatinine, and e-GFR. Conclusion: The urinary NAG can be used as an early urinary biomarker for early detection and progression of diabetic nephropathy in type 2 diabetic patients.

Metabolomic differences of seminal plasma between boars with high and low average conception rates after artificial insemination.

Seminal plasma is a complex biological fluid containing many metabolites including amino acids, fructose, carbohydrates and lipids Metabolites play important roles in multiple biological processes, but details and significance of the seminal plasma metabolome related to boar fertility are unknown. The aim of the present study was to compare the comprehensive metabolome of seminal plasma from boars with different conception rate after artificial insemination and to identify the potential biomarkers. Semen samples were collected from boars which divided into two groups according to the conception rates in the offspring. Seminal plasma metabolites were isolated, purified, and then subjected to Ultra-high Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-qTOF-MS) procession. A total of 576 (Positive ion mode) and 377 (Negative ion mode) metabolites were identified in seminal plasma. Metabolites were identified and categorized according to their major chemical classes, including carboxylic acids and derivatives, organooxygen compounds, amino acids, peptides, and alogues, fatty amides, fatty acyls, benzene and substituted derivatives, purine nucleotides, pyrimidine nucleotides, glycosyl compounds, fatty acids and conjugates. The results showed that 4-Aminobenzoate, Pro-Asn, Ile-Tyr, Homoveratric acid and D-Biotin were higher in semen of boar with higher conception rate (HG) versus lower conception rate (LG) (p<.05), whereas L-Serine, Butoxyacetic acid, S-Methyl-5'-thioadenosine, Capsaicin and 1-O-(cis-9-Octadecenyl)-2-O-acetyl-sn-glycero-3-phosphocholine (PAF) were lower in HG than in LG (p<.05). These metabolites may be considered as candidate biomarkers for different fertility in boars.

Effect of unsaturated fatty acids on glycation product formation pathways (Ⅰ) the role of oleic acid

Research on advanced glycation end-products (AGEs) and their formation pathways in food processing has gradually increased because AGEs are associated with human health, especially with involvement of lipids. In this study, radicals and glycation products were detected via electron spin resonance (ESR) and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) respectively. The correlation of important intermediates was used to explain the effect of oleic acid (OA) on the glycation products and pathways. The results indicated OA participation decreased the content of stable radicals and glycosyl compounds in Maillard Reaction (MR). The oxidation of OA produced active radicals, and electron transfer caused lysine to transform radical form. These radicals participated in the formation of fructosyllysine (FL) with glucose (Glc) via the MR. The participation of OA is acted as inhibiting the way of Glc autoxidation and promoting the glycation pathway from FL to 3-deoxyglucosone (3-DG) to fluorescent-AGEs. Orthogonal projection to latent structures discriminant analysis results indicated that 3-DG, D-glucosone and methylglyoxal are key products in discriminating the glycation reaction.

Identification of α-Amyrin 28-Carboxylase and Glycosyltransferase From Ilex asprella and Production of Ursolic Acid 28-O-β-D-Glucopyranoside in Engineered Yeast.

Ilex asprella is a medicinal plant that is used extensively in southern China. The plant contains ursane-type triterpenoids and triterpenoid saponins which are known to be responsible for its pharmacological activities. Previously, a transcriptomic analysis of I. asprella was carried out and the gene IaAS1, which is important in the formation of the core structure α-amyrin, was identified. However, the genes related to the subsequent derivatization of the core structures of the triterpenoid remain largely unknown. Herein, we describe the cloning and functional characterization of an amyrin 28-carboxylase IaAO1 (designated as IaCYP716A210) and a glycosyltransferase IaAU1 (designated as UGT74AG5), based on transcriptomic data. The expression of IaAO1 in an α-amyrin producing yeast strain led to the accumulation of ursolic acid. An enzyme assay using recombinant protein IaAU1 purified from E. coli revealed that IaAU1 can catalyze the conversion of ursolic acid to ursolic acid 28-O-β-D-glucopyranoside. IaAU1 has regiospecificity for catalyzing the 28-O-glucosylation of ursane-/oleanane-type triterpene acids, as it can also catalyze the conversion of oleanolic acid, hederagenin, and ilexgenin A to their corresponding glycosyl compounds. Moreover, co-expression of IaAO1 and IaAU1 in the α-amyrin-producing yeast strain led to the production of ursolic acid 28-O-β-D-glucopyranoside, although in relatively low amounts. Our study reveals that IaAO1 and IaAU1 might play a role in the biosynthesis of pentacyclic triterpenoid saponins in I. asprella and provides insights into the potential application of metabolic engineering to produce ursane-type triterpene glycosides.

Electrochemically prepared poly(L-lysine) and 3-hydroxyphenylboronic acid composite as a conventional adhesion material for rice suspension cells

Poly(L-lysine) (PLL)-3-hydroxyphenylboronic acid (3-PBA) composite was prepared onto an Au electrode via cyclic voltammetry (CV), which was characterized by electrochemical and quartz crystal microbalance (QCM) techniques, and used to promote adhesion of plant cells. 3-PBA can interact with glycosyl compounds on the cell wall to form negatively charged covalent compounds while PLL increases the number of positively charged sites, which enhances the electrostatic interactions with the negatively charged cell wall, both promoting cell adhesion. The PLL-poly(3-PBA) composite was successfully modified on the Au electrode surface, as demonstrated by QCM and Fourier transform infrared spectrophotometry (FTIR). Moreover, we confirmed the synergistic effect of PLL and 3-PBA to adhere rice suspension cells using CV, electrochemical impedance spectroscopy (EIS), QCM and optical microscope observations. Finally, the dynamic process of rice cells’ adhesion to PLL-poly(3-PBA)/Au followed by salt stress treatment of NaCl was monitored in real-time by QCM. The cells softened at first then hardened under the action of 40 mM NaCl. This work presents a novel and conventional way to immobilize plant cells onto sensors, and has importance in the study of the structure, function and behavior of plants under various stresses at the cellular level.

Value-added carbohydrate building blocks by regioselective O-alkylation of C-glucosyl compounds

Functionalized carbohydrates and especially functionalized C-glycosides are useful intermediates for the synthesis of complex carbohydrates of interest. In this paper, we describe the synthesis of C-azidopropylglucopyranosides and give a full account of their regioselective acylation and alkylation. Alkylation of these C-glucosyl compounds containing 1,2-trans-diol, namely 2- and 3-OH were first optimized with benzyl bromide. The reaction has then been extended to various electrophiles thus providing 3-O-substituted C-glucosyl compounds. These results are one of the first examples of regioselective alkylation with functionalized electrophiles on glycosyl compounds featuring a trans-vicinal diol. Furthermore, we describe some results obtained during regioselective deprotection of 4,6-O-benzylidene protecting group. This work opens the way to the synthesis of complex carbohydrate derivatives.