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Nature Aug 2022The identification of general and efficient methods for the construction of oligosaccharides stands as one of the great challenges for the field of synthetic chemistry....
The identification of general and efficient methods for the construction of oligosaccharides stands as one of the great challenges for the field of synthetic chemistry. Selective glycosylation of unprotected sugars and other polyhydroxylated nucleophiles is a particularly significant goal, requiring not only control over the stereochemistry of the forming bond but also differentiation between similarly reactive nucleophilic sites in stereochemically complex contexts. Chemists have generally relied on multi-step protecting-group strategies to achieve site control in glycosylations, but practical inefficiencies arise directly from the application of such approaches. Here we describe a strategy for small-molecule-catalyst-controlled, highly stereo- and site-selective glycosylations of unprotected or minimally protected mono- and disaccharides using precisely designed bis-thiourea small-molecule catalysts. Stereo- and site-selective galactosylations and mannosylations of a wide assortment of polyfunctional nucleophiles is thereby achieved. Kinetic and computational studies provide evidence that site-selectivity arises from stabilizing C-H/π interactions between the catalyst and the nucleophile, analogous to those documented in sugar-binding proteins. This work demonstrates that highly selective glycosylation reactions can be achieved through control of stabilizing non-covalent interactions, a potentially general strategy for selective functionalization of carbohydrates.
Topics: Catalysis; Chemistry Techniques, Synthetic; Disaccharides; Glycosylation; Kinetics; Monosaccharides; Stereoisomerism; Sugars
PubMed: 35709829
DOI: 10.1038/s41586-022-04958-w -
Bioconjugate Chemistry Aug 2022Methylcyclopropene (Cyoc)-tagged tetra-acetylated monosaccharides, and in particular mannosamine derivatives, are promising tools for medical imaging of cancer using...
Methylcyclopropene (Cyoc)-tagged tetra-acetylated monosaccharides, and in particular mannosamine derivatives, are promising tools for medical imaging of cancer using metabolic oligosaccharide engineering and the extremely fast inverse electron-demand Diels-Alder bioorthogonal reaction. However, the potential of these monosaccharide derivatives has yet to be fully explored due to their low aqueous solubility. To address this issue, we sought to vary the extent of acetylation of Cyoc-tagged monosaccharides and probe its effect on the extent of glycan labeling in various cancer cell lines. We demonstrate that, in the case of AcManNCyoc, tri- and diacetylated derivatives generated significantly enhanced cell labeling compared to the tetra-acetylated monosaccharide. In contrast, for the more readily soluble azide-tagged sugars, a decrease in acetylation led to decreased glycan labeling. AcManNCyoc gave better labeling than the azido-tagged AcManNAz and has significant potential for and imaging of glycosylated cancer biomarkers.
Topics: Acetylation; Monosaccharides; Neoplasms; Polysaccharides; Staining and Labeling
PubMed: 35876696
DOI: 10.1021/acs.bioconjchem.2c00169 -
Journal of Bacteriology Sep 1971Cell walls of Histoplasma capsulatum and Blastomyces dermatitidis, obtained by mechanical breakage of yeast- and mycelial-phase cultures, were lipid-extracted and then...
Cell walls of Histoplasma capsulatum and Blastomyces dermatitidis, obtained by mechanical breakage of yeast- and mycelial-phase cultures, were lipid-extracted and then fractionated with ethylenediamine. Unextracted cell walls, lipid-extracted cell walls, and the three fractions resulting from ethylenediamine treatment were examined for monosaccharide and chitin content. The yeast-phase cell walls of five strains of H. capsulatum fell into two categories, designated chemotypes I and II, one of which, chemotype II, was similar to yeast-phase cell walls derived from three strains of B. dermatitidis. H. capsulatum chemotype I cell walls were characterized by lower content of material soluble in ethylenediamine, higher chitin content, and lower monosaccharide content than H. capsulatum chemotype II or B. dermatitidis cell walls. Approximately 80% of the monosaccharides of chemotype I cell walls was combined in forms susceptible to attack by mild acid hydrolysis, compared with about 50% of the monosaccharides of chemotype II and B. dermatitidis. H. capsulatum and B. dermatitidis yeast-phase cell walls could be distinguished, however, by their susceptibility to attack by a crude enzyme system derived from a Streptomyces sp. incubated with chitin as the only carbon source. Both glucose and acetylglucosamine were released from H. capsulatum cell walls, regardless of chemotype, during enzymatic hydrolysis, whereas only acetylglucosamine was released from B. dermatitidis yeast-phase cell walls. Mycelial-phase cell walls of H. capsulatum and B. dermatitidis were characterized by lower content of material soluble in ethylenediamine, higher proportions of mannose, and lower chitin content than their respective yeast phases. Glucose and acetylglucosamine were both released from all mycelial-phase cell walls, whether H. capsulatum or B. dermatitidis, by the crude enzyme system.
Topics: Bile Acids and Salts; Blastomyces; Cell Wall; Chitin; Chitinases; Chromatography, Gas; Ethylenediamines; Glucosamine; Glucose; Glycoside Hydrolases; Histoplasma; Hydrochloric Acid; Hydrolysis; Mannose; Monosaccharides; Saccharomyces; Solvents; Species Specificity; Streptomyces
PubMed: 5095293
DOI: 10.1128/jb.107.3.870-877.1971 -
Biomedicine & Pharmacotherapy =... Oct 2023Long-acting and specific targeting are two important properties of excellent drug delivery systems. Currently, the long-acting strategies based on polyethylene glycol... (Review)
Review
Long-acting and specific targeting are two important properties of excellent drug delivery systems. Currently, the long-acting strategies based on polyethylene glycol (PEG) are controversial, and PEGylation is incapable of simultaneously possessing targeting ability. Thus, it is crucial to identify and develop approaches to produce long-acting and targeted drug delivery systems. Sialic acid (SA) is an endogenous, negatively charged, nine-carbon monosaccharide. SA not only mediates immune escape in the body but also binds to numerous disease related targets. This suggests a potential strategy, namely "sialylation," for preparing long-acting and targeted drug delivery systems. This review focuses on the application status of SA-based long-acting and targeted agents as a reference for subsequent research.
Topics: Carbon; Drug Delivery Systems; Monosaccharides; N-Acetylneuraminic Acid; Polyethylene Glycols
PubMed: 37611437
DOI: 10.1016/j.biopha.2023.115353 -
Molecules (Basel, Switzerland) Aug 2022PMP-HPLC, FT-IR, and HPSEC fingerprints of 10 batches of polysaccharides from with different production areas and harvest times have been prepared, and the chemometrics...
PMP-HPLC, FT-IR, and HPSEC fingerprints of 10 batches of polysaccharides from with different production areas and harvest times have been prepared, and the chemometrics analysis was performed. The anti-allergic activity of 10 batches of polysaccharide (SP) was evaluated, and the spectrum-effect relationship of the 10 batches of SP was analyzed by gray correlation degree with the chromatographic fingerprint as the independent variable. The results showed that the PMP-HPLC, HPSEC, and FT-IR fingerprints of 10 batches of SP had a high similarity. Two monosaccharides (rhamnose and galactose), the polysaccharide fragment Mn = 8.67 × 10~9.56 × 10 Da, and the FT-IR absorption peak of 892 cm can be used as the quality control markers of SPs. All 10 batches of SP could significantly inhibit the release of β-HEX in RBL-231 cells, and the polysaccharides harvested from Inner Mongolia in the winter had the best anti-allergic activity. The spectrum-effect relationship model showed that the monosaccharide composition and molecular weight were related to the anti-allergic activity of the SPs. Multiple fingerprints combined with spectrum-effect relationship analysis can evaluate and control the quality of SPs from the aspects of overall quality and efficacy, which has more application value.
Topics: Anti-Allergic Agents; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Monosaccharides; Plant Roots; Polysaccharides; Spectroscopy, Fourier Transform Infrared
PubMed: 36014516
DOI: 10.3390/molecules27165278 -
Chemical Reviews Oct 2022Fluorinated carbohydrates have found many applications in the glycosciences. Typically, these contain fluorination at a single position. There are not many applications... (Review)
Review
Fluorinated carbohydrates have found many applications in the glycosciences. Typically, these contain fluorination at a single position. There are not many applications involving polyfluorinated carbohydrates, here defined as monosaccharides in which more than one carbon has at least one fluorine substituent directly attached to it, with the notable exception of their use as mechanism-based inhibitors. The increasing attention to carbohydrate physical properties, especially around lipophilicity, has resulted in a surge of interest for this class of compounds. This review covers the considerable body of work toward the synthesis of polyfluorinated hexoses, pentoses, ketosugars, and aminosugars including sialic acids and nucleosides. An overview of the current state of the art of their glycosidation is also provided.
Topics: Fluorine; Carbohydrates; Hexoses; Pentoses; Monosaccharides; Nucleosides; Sialic Acids; Carbon
PubMed: 35613331
DOI: 10.1021/acs.chemrev.2c00086 -
FEBS Letters May 2007The availability of complete plant genomes has greatly influenced the identification and analysis of phylogenetically related gene clusters. In Arabidopsis, this has... (Review)
Review
The availability of complete plant genomes has greatly influenced the identification and analysis of phylogenetically related gene clusters. In Arabidopsis, this has revealed the existence of a monosaccharide transporter(-like) gene family with 53 members, which play a role in long-distance sugar partitioning or sub-cellular sugar distribution and catalyze the transport of hexoses, but also polyols and in one case also pentoses and tetroses. An update on the currently available information on these Arabidopsis monosaccharide transporters, on their sub-cellular localization and physiological function will be given.
Topics: Arabidopsis; Arabidopsis Proteins; Genes, Plant; Models, Biological; Monosaccharide Transport Proteins; Monosaccharides; Multigene Family; Phylogeny; Plants
PubMed: 17379213
DOI: 10.1016/j.febslet.2007.03.016 -
Chimia 2011Since the discovery of the 'formose reaction' by Butlerow, total synthesis of carbohydrates has undergone rapid development. The most important methods for the... (Review)
Review
Since the discovery of the 'formose reaction' by Butlerow, total synthesis of carbohydrates has undergone rapid development. The most important methods for the asymmetric synthesis of monosaccharides and analogues of biological importance are presented. Nowadays any natural and non-natural monosaccharide can be prepared pure in both enantiomeric forms starting from inexpensive starting materials. Metal-based asymmetric catalysis and organocatalysis have been successfully applied, alone or in combination with chemoenzymatic methods. Alternative methods rely upon substrate- or reagent-controlled diastereo- and enantioselective reactions. Suitably protected carbohydrates have been prepared by total synthesis, thus allowing their direct use in the preparation of oligosaccharides and analogues.
Topics: Molecular Structure; Monosaccharides; Stereoisomerism
PubMed: 21469452
DOI: 10.2533/chimia.2011.85 -
Applied and Environmental Microbiology Jan 2024FAD-dependent pyranose oxidase (POx) and -glycoside-3-oxidase (CGOx) are both members of the glucose-methanol-choline superfamily of oxidoreductases and belong to the...
FAD-dependent pyranose oxidase (POx) and -glycoside-3-oxidase (CGOx) are both members of the glucose-methanol-choline superfamily of oxidoreductases and belong to the same sequence space. Pyranose oxidases had been studied for their oxidation of monosaccharides such as D-glucose, but recently, a bacterial -glycoside-3-oxidase that is phylogenetically related to POx and that reacts with -glycosides such as carminic acid, mangiferin or puerarin has been described. Since these actinobacterial CGOx enzymes belong to the same sequence space as bacterial POx, they must have evolved from the same ancestor. Here, we performed a phylogenetic analysis of actinobacterial sequences and resurrected seven ancestral enzymes of the POx/CGOx sequence space to study the evolutionary trajectory of substrate preferences for monosaccharides and -glycosides. Clade I, with its dimeric member POx from , shows strict preference for monosaccharides (D-glucose and D-xylose) and does not react with any of the glycosides tested. No extant member of clade II has been studied to date. The two extant members of clades III and IV, monomeric POx/CGOx from and , oxidized both monosaccharides as well as various -glycosides (homoorientin, isovitexin, mangiferin, and puerarin). Steady-state kinetic parameters of several clades III and IV ancestral enzymes indicate that the generalist ancestor N35 slowly evolved to present-day enzymes with a much higher preference for -glycosides than monosaccharides. Based on structural predictions of ancestors, we hypothesize that the strict specificity of bacterial clade I POx (and also fungal POx) is the result of oligomerization, which in turn results from the evolution of protein segments that were shown to be important for oligomerization, the arm, and the head domain.IMPORTANCE-Glycosides often form active compounds in various plants. Breakage of the C-C bond in these glycosides to release the aglycone is challenging and proceeds via a two-step reaction, the oxidation of the sugar and subsequent cleavage of the C-C bond. Recently, an enzyme from a soil bacterium, FAD-dependent -glycoside-3-oxidase (CGOx), was shown to catalyze the initial oxidation reaction. Here, we show that CGOx belongs to the same sequence space as pyranose oxidase (POx), and that an actinobacterial ancestor of the POx/CGOx family evolved into four clades, two of which show a high preference for -glycosides.
Topics: Oxidoreductases; Phylogeny; Glycosides; Monosaccharides; Glucose
PubMed: 38179968
DOI: 10.1128/aem.01676-23 -
Microbial Genomics Nov 2020Several monosaccharides constitute naturally occurring glycans, but it is uncertain whether they constitute a universal set like the alphabets of proteins and DNA. Based...
Several monosaccharides constitute naturally occurring glycans, but it is uncertain whether they constitute a universal set like the alphabets of proteins and DNA. Based on the available experimental observations, it is hypothesized herein that the glycan alphabet is not universal. Data on the presence/absence of pathways for the biosynthesis of 55 monosaccharides in 12 939 completely sequenced archaeal and bacterial genomes are presented in support of this hypothesis. Pathways were identified by searching for homologues of biosynthesis pathway enzymes. Substantial variations were observed in the set of monosaccharides used by organisms belonging to the same phylum, genera and even species. Monosaccharides were grouped as common, less common and rare based on their prevalence in Archaea and Bacteria. It was observed that fewer enzymes are sufficient to biosynthesize monosaccharides in the common group. It appears that the common group originated before the formation of the three domains of life. In contrast, the rare group is confined to a few species in a few phyla, suggesting that these monosaccharides evolved much later. Fold conservation, as observed in aminotransferases and SDR (short-chain dehydrogenase reductase) superfamily members involved in monosaccharide biosynthesis, suggests neo- and sub-functionalization of genes led to the formation of the rare group monosaccharides. The non-universality of the glycan alphabet begets questions about the role of different monosaccharides in determining an organism's fitness.
Topics: Archaea; Bacteria; Carbonyl Reductase (NADPH); Genome, Archaeal; Genome, Bacterial; Metabolic Networks and Pathways; Monosaccharides; Polysaccharides; Transaminases
PubMed: 33048043
DOI: 10.1099/mgen.0.000452