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Analytica Chimica Acta May 2022Glycans are ubiquitous, structurally diverse molecules that have specific and general roles involving metabolism, structure, and cell-to-cell signaling. Functional...
Glycans are ubiquitous, structurally diverse molecules that have specific and general roles involving metabolism, structure, and cell-to-cell signaling. Functional specificity depends strongly on the complexity of structures that polysaccharides can adopt based on their subunit composition, length, extent of branching, glycosidic bond connectivity and anomeric configuration. However, a rapid and comprehensive characterization of glycan isomers can be challenging owing to limitations associated with their separation. Here, ten composition, anomeric and connectivity disaccharide isomers were separated and detected using high-resolution differential ion mobility-mass spectrometry (DMS-MS, also known as FAIMS). Focus was primarily directed to compositional isomers corresponding to epimers that differ by the axial or equatorial position of a single hydroxyl group. DMS resolving power was enhanced 14-fold primarily by increasing the fraction of helium in the ion carrier gas and lowering the flow rate. At relatively high disaccharide concentrations, DMS-MS of each disaccharide resulted in complex and unique multi-peak spectra with up to ten fully and partially resolved peaks for β-1,4-mannobiose (Man-1,4β-Man), which can be attributed to the DMS separation and subsequent dissociation of ionic non-covalently bound oligomers into monomer ions. Each DMS spectrum has at least one differentiating peak that is not in the other spectra, indicating that DMS can be used to fully or partially resolve composition, configuration and connectivity isomers. At relatively low disaccharide concentrations, mixtures of disaccharide epimers can also be readily separated by DMS. The integration of high-resolution, ambient pressure DMS with complementary reduced-pressure ion mobility and MS-based glycomics and glycoproteomics workflows may be useful for improving the characterization of glycans and glycosylated biomolecules.
Topics: Disaccharides; Humans; Ions; Isomerism; Mass Spectrometry
PubMed: 35473855
DOI: 10.1016/j.aca.2022.339783 -
Yakugaku Zasshi : Journal of the... 2021Two novel β-trefoil lectins, MytiLec-1 and SeviL were found from mussels in the coast of Yokohama and Nagasaki. MytiLec-1 was purified from gill and mantle of Mytilus... (Review)
Review
Two novel β-trefoil lectins, MytiLec-1 and SeviL were found from mussels in the coast of Yokohama and Nagasaki. MytiLec-1 was purified from gill and mantle of Mytilus galloprovincialis. It was consisted of 149 amino acid residues and there was no similarity with any other proteins when it was discovered. We advocate for this "Mytilectin" as a new protein family because of their novelty of its primary structure and homologues were also found in other mussels. Glycan array analysis revealed that MytiLec-1 specifically bound to the Gb3 and Gb4 glycan which contained the α-galactoside. MytiLec-1 caused the apoptosis against the Burkitt's lymphoma cells through the interaction of Gb3 express in their cell surface. On the other hand, SeviL obtained from gill and mantle of Mytilisepta virgata showed the specific binding against GM1b, asialo GM1 and SSEA-4 which are known as glycosphingolipid glycan including the β-galactoside. In addition, SeviL was identified as R type lectin by confirmation of QXW motif within its primary structure. Messenger RNA of SeviL like R type lectins was also found among the musssels including Mytilus galloprovincialis. SeviL also showed the apoptosis against asialo GM1 expressing cells. To apply the anticancer lectin as a novel molecular target drug, primary structure of MytiLec-1 was analyzed to enhance the stabilization of confirmation by computational design technique. It was succeeded to produce a monomeric artificial β-trefoil lectin, Mitsuba-1 without losing the Gb3 binding ability. Comparison of biological function between Mitsuba-1 and MytiLec-1 is also described in this study.
Topics: Animals; Antineoplastic Agents; Burkitt Lymphoma; Disaccharides; Drug Design; Galectins; Lectins; Molecular Conformation; Molecular Targeted Therapy; Mytilidae; Polysaccharides; Tandem Repeat Sequences; Trisaccharides
PubMed: 33790114
DOI: 10.1248/yakushi.20-00215 -
Bioproduction and applications of aldobionic acids with a focus on maltobionic and cellobionic acid.Bioprocess and Biosystems Engineering Jul 2023Aldobionic acids are sugar acids which consist of a disaccharide with an anomeric acid group. The most famous is lactobionic acid (LBA). LBA is used in many applications... (Review)
Review
Aldobionic acids are sugar acids which consist of a disaccharide with an anomeric acid group. The most famous is lactobionic acid (LBA). LBA is used in many applications such as food and beverages, pharmaceuticals and medicine, cosmetics or chemical processes. During the last decade, all these industries are observing a shift of consumer preferences towards plant-based options. Thus, the biotechnological industry is trying to replace the animal-derived LBA. Maltobionic acid (MBA) and cellobionic acid (CBA) are two stereoisomers of LBA which have emerged as vegan alternatives. However, MBA and CBA face different obstacles related to their industrial production. While traditionally used electrochemical or chemical catalysis often rely on cost intensive and/or hazardous catalysts, novel production methods with microorganisms are still poorly studied. In the first part, this paper discusses both alternatives in terms of their characteristics and applications. In the second part, it reviews the long-studied chemical production and the novel bioproduction methods, which are based on enzymatic and microbial systems. This review concludes with a discussion of future work needed to bring their production to the industrial scale.
Topics: Animals; Disaccharides; Biotechnology
PubMed: 37058246
DOI: 10.1007/s00449-023-02872-7 -
Proteomics Dec 2016Galactoseβ1-4fucose (Galβ1-4Fuc), a unique disaccharide unit found only on the N-glycans of Protostomia, has been intensively studied, particularly in Nematoda.... (Review)
Review
Galactoseβ1-4fucose (Galβ1-4Fuc), a unique disaccharide unit found only on the N-glycans of Protostomia, has been intensively studied, particularly in Nematoda. Galβ1-4Fuc attached to the 6-OH of the innermost GlcNAc of N-glycans has been identified as an endogenous target recognized by Caenorhabditis elegans galectin LEC-6 and might function as an endogenous ligand for other galectins as well. Interactions between galectins and N-glycans might be subject to fine-tuning through modifications of the penultimate GlcNAc and the Galβ1-4Fuc unit. Similar fine-tuning is also observable in vertebrate galectins, although their major recognition unit is a Galβ1-4GlcNAc. In Protostomia, it can be postulated that glycan-binding proteins and their ligands have coevolved; however, epitopes such as Galβ1-4Fuc were then hijacked as targets by other organisms. Fungal (Coprinopsis cinerea) galectin 2, CGL2, binds the Galβ1-4Fuc on C. elegans glycans to exert its nematotoxicity. Some human and mouse galectins bind to synthesized Galβ1-4Fuc; as some parasitic nematodes express this motif, its recognition by mammalian galectins could hypothetically be involved in host defense, similar to fungal CGL2. In this review, we discuss the Galβ1-4Fuc unit in Protostomia as a possible equivalent for the Galβ1-4GlcNAc unit in vertebrates and a potential non-self glycomarker useful for pathogen recognition.
Topics: Amino Acid Sequence; Animals; Biosynthetic Pathways; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Disaccharides; Galectins; Invertebrates; Molecular Docking Simulation; Polysaccharides; Sequence Alignment
PubMed: 27091793
DOI: 10.1002/pmic.201600001 -
Organic & Biomolecular Chemistry Apr 2020S-Glycosides are important tools for the elucidation of specific protein-carbohydrate interactions and can significantly aid structural and functional studies of...
S-Glycosides are important tools for the elucidation of specific protein-carbohydrate interactions and can significantly aid structural and functional studies of carbohydrate-active enzymes, as they are often inert or act as enzyme inhibitors. In this context, this work focuses on the introduction of an S-linkage into arabinoxylan oligosaccharides (AXs) in order to obtain a small collection of synthetic tools for the study of AXs degrading enzymes. The key step for the introduction of the S-glycosidic linkage involved anomeric thiol S-alkylation of an orthogonally protected l-arabinopyranoside triflate. The resulting S-linked disaccharide was subsequently employed in a series of glycosylation reactions to obtain a selectively protected tetrasaccharide. This could be further elaborated through chemoselective deprotection and glycosylation reactions to introduce branching l-arabinofuranosides.
Topics: Arabinose; Cross-Linking Reagents; Disaccharides; Glycosides; Glycosylation; Oligosaccharides; Sulfhydryl Compounds; Xylans
PubMed: 32206767
DOI: 10.1039/d0ob00470g -
Talanta Nov 2022Glycans are the most abundant organic polymers in nature. They are essential to living organisms and regulate a wide range of biological functions. However, mass...
Glycans are the most abundant organic polymers in nature. They are essential to living organisms and regulate a wide range of biological functions. However, mass spectrometry-based identification of glycan isomers remains challenging due to the complexity of their structures including their complex compositions, linkages, and anomeric configurations. In this study, two novel complex ions, the mononuclear copper-bound dimeric ions [(Cu)(A)(L-His)-H] and the mononuclear copper-bound quaternary ions [(Cu)(A)(L-Ser)-H] (where A denotes a disaccharide, and L-Ser/His denotes l-serine/histidine), were designed for the collision-induced dissociation-based identification and relative quantification of 14 disaccharide isomers. When the unique fragmentation patterns of the above two types of complex ions were mapped into a three-dimensional vector, all the isomers were completely distinguished. Of note, the established method is able to identify mixtures of linkage isomers only using tandem mass spectrometry based on linkage-specific fragment ions of histidine-based complex ions. Finally, the method was successfully applied to the identification and relative quantification of two disaccharide isomers (lactose and sucrose) in dairy beverages. In conclusion, the established method is sensitive to subtle structural differences in disaccharide isomers and has the potential to be used for the differentiation of various glycans.
Topics: Copper; Disaccharides; Histidine; Ions; Isomerism; Polysaccharides; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 35717753
DOI: 10.1016/j.talanta.2022.123674 -
Biochemical and Biophysical Research... Jul 2022Chondroitin sulfate (CS) and heparan sulfate (HS) are sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide units composed of hexosamine and...
Chondroitin sulfate (CS) and heparan sulfate (HS) are sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide units composed of hexosamine and hexuronic acid. GAG chains exhibit diverse bioactivities in a structure-specific manner. Marine invertebrates are a rich source of highly sulfated and rare structures of GAG chains. Here, we isolated GAGs from the green-lipped mussel Perna canaliculus, an aquaculture species that is produced on a large scale. We separated GAGs based on the degree of negative charges and analyzed their disaccharide compositions. CS and HS both exhibited characteristic compositions of differently sulfated disaccharides. CS chains showed a higher degree of sulfation than HS chains and contained a high percentage of the E unit disaccharide GlcA-GalNAc(4,6-O-disulfate). Furthermore, CS chains rich in the E unit stimulated the neurite outgrowth of primary cultured neurons. The present results indicate the potential of P. canaliculus GAGs as biomaterials to study the structure-function relationships of GAGs.
Topics: Animals; Chondroitin Sulfates; Disaccharides; Glycosaminoglycans; Heparitin Sulfate; Perna; Sulfates
PubMed: 35504089
DOI: 10.1016/j.bbrc.2022.04.095 -
Biomacromolecules Jun 2021Antifreeze glycoproteins (AFGPs) are able to bind to ice, halt its growth, and are the most potent inhibitors of ice recrystallization known. The structural basis for...
Antifreeze glycoproteins (AFGPs) are able to bind to ice, halt its growth, and are the most potent inhibitors of ice recrystallization known. The structural basis for AFGP's unique properties remains largely elusive. Here we determined the antifreeze activities of AFGP variants that we constructed by chemically modifying the hydroxyl groups of the disaccharide of natural AFGPs. Using nuclear magnetic resonance, two-dimensional infrared spectroscopy, and circular dichroism, the expected modifications were confirmed as well as their effect on AFGPs solution structure. We find that the presence of all the hydroxyls on the disaccharides is a requirement for the native AFGP hysteresis as well as the maximal inhibition of ice recrystallization. The saccharide hydroxyls are apparently as important as the acetyl group on the galactosamine, the α-linkage between the disaccharide and threonine, and the methyl groups on the threonine and alanine. We conclude that the use of hydrogen-bonding through the hydroxyl groups of the disaccharide and hydrophobic interactions through the polypeptide backbone are equally important in promoting the antifreeze activities observed in the native AFGPs. These important criteria should be considered when designing synthetic mimics.
Topics: Antifreeze Proteins; Disaccharides; Glycoproteins; Hydrogen Bonding; Ice; Magnetic Resonance Spectroscopy
PubMed: 33957041
DOI: 10.1021/acs.biomac.1c00313 -
Angewandte Chemie (International Ed. in... Mar 2020C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics. We demonstrate that activating a hemiacetal with a sulfonyl...
C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics. We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides. This reaction tolerates a range of acceptors and donors, including disaccharides. The resulting products can be readily derivatized into C-glycoside analogues of β-glycoconjugates, including C-disaccharide mimetics.
Topics: Alkylation; Disaccharides; Glycoconjugates; Glycosides; Glycosylation; Molecular Structure; Stereoisomerism; Sulfinic Acids
PubMed: 31880395
DOI: 10.1002/anie.201914221 -
Journal of the American Chemical Society Jul 2015The total synthesis of the rare but extremely potent antitumor agent shishijimicin A has been achieved via a convergent strategy involving carboline disaccharide 3 and...
The total synthesis of the rare but extremely potent antitumor agent shishijimicin A has been achieved via a convergent strategy involving carboline disaccharide 3 and hydroxy enediyne thioacetate 4.
Topics: Antineoplastic Agents; Biological Products; Carbolines; Disaccharides; Enediynes; Sulfhydryl Compounds
PubMed: 26133230
DOI: 10.1021/jacs.5b05575