Molecules

2024

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18 pages, 4115 KiB

Open AccessReview

ZnI₂-Mediated cis-Glycosylations of Various Constrained Glycosyl Donors: Recent Advances in cis-Selective Glycosylations

by Akihiro Ishiwata, Xuemei Zhong, Katsunori Tanaka, Yukishige Ito and Feiqing Ding

Molecules 2024, 29(19), 4710; https://doi.org/10.3390/molecules29194710 - 4 Oct 2024

Viewed by 1020

Abstract

An efficient and versatile glycosylation methodology is crucial for the systematic synthesis of oligosaccharides and glycoconjugates. A direct intermolecular and an indirect intramolecular methodology have been developed, and the former can be applied to the synthesis of medium-to-long-chain glycans like that of nucleotides [...] Read more.

An efficient and versatile glycosylation methodology is crucial for the systematic synthesis of oligosaccharides and glycoconjugates. A direct intermolecular and an indirect intramolecular methodology have been developed, and the former can be applied to the synthesis of medium-to-long-chain glycans like that of nucleotides and peptides. The development of a generally applicable approach for the stereoselective construction of glycosidic bonds remains a major challenge, especially for the synthesis of 1,2-cis glycosides such as β-mannosides, β-L-rhamnosides, and β-D-arabinofuranosides with equatorial glycosidic bonds as well as α-D-glucosides with axial ones. This review introduces the direct formation of cis-glycosides using ZnI₂-mediated cis-glycosylations of various constrained glycosyl donors, as well as the recent advances in the development of stereoselective cis-glycosylations. Full article

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43 pages, 9236 KiB

Open AccessArticle

Exploring and Re-Assessing Reverse Anomeric Effect in 2-Iminoaldoses Derived from Mono- and Polynuclear Aromatic Aldehydes

by Esther M. S. Pérez, Esther Matamoros, Pedro Cintas and Juan C. Palacios

Molecules 2024, 29(17), 4131; https://doi.org/10.3390/molecules29174131 - 30 Aug 2024

Viewed by 458

Abstract

A curious and noticeable structural feature in Schiff bases from 2-aminoaldoses is the fact that imino tautomers arranged equatorially in the most stable ring conformation exhibit a counterintuitive reverse anomeric effect (RAE) in the mutarotational equilibrium, i.e., the most stable and abundant anomer [...] Read more.

A curious and noticeable structural feature in Schiff bases from 2-aminoaldoses is the fact that imino tautomers arranged equatorially in the most stable ring conformation exhibit a counterintuitive reverse anomeric effect (RAE) in the mutarotational equilibrium, i.e., the most stable and abundant anomer is the equatorial one (β). As shown by our very recent research, this effect arises from the total or partial inhibition of the exo-anomeric effect due to the presence of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen in the axial anomer (α). When the Schiff base adopts either an enamine structure or the imino group is protonated, the exo-anomeric effect is restored, and the axial α-anomer becomes the most stable species. Although the intramolecular H-bonding should appropriately be interpreted as a genuine stereoelectronic effect, the magnitude of the RAE could be affected by other structural parameters. Herein and through a comprehensive analysis of benzylidene, cinnamylidene, naphthalene, phenanthrene, and anthracene aldehydes, we show the robustness of the RAE effect, which is similar in extent to simple aldehydes screened so far, irrespective of the size and/or hydrophobicity of the substituent at the nitrogen atom. Full article

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39 pages, 3668 KiB

Open AccessReview

Progress on the Anti-Inflammatory Activity and Structure–Efficacy Relationship of Polysaccharides from Medical and Edible Homologous Traditional Chinese Medicines

by Yuanyuan Zhang, Xiulian Lin, Li Xia, Suhui Xiong, Bohou Xia, Jingchen Xie, Yan Lin, Limei Lin and Ping Wu

Molecules 2024, 29(16), 3852; https://doi.org/10.3390/molecules29163852 - 14 Aug 2024

Viewed by 1647

Abstract

Medicinal food varieties developed according to the theory of medical and edible homologues are effective at preventing and treating chronic diseases and in health care. As of 2022, 110 types of traditional Chinese medicines from the same source of medicine and food have [...] Read more.

Medicinal food varieties developed according to the theory of medical and edible homologues are effective at preventing and treating chronic diseases and in health care. As of 2022, 110 types of traditional Chinese medicines from the same source of medicine and food have been published by the National Health Commission. Inflammation is the immune system’s first response to injury, infection, and stress. Chronic inflammation is closely related to many diseases such as atherosclerosis and cancer. Therefore, timely intervention for inflammation is the mainstay treatment for other complex diseases. However, some traditional anti-inflammatory drugs on the market are commonly associated with a number of adverse effects, which seriously affect the health and safety of patients. Therefore, the in-depth development of new safe, harmless, and effective anti-inflammatory drugs has become a hot topic of research and an urgent clinical need. Polysaccharides, one of the main active ingredients of medical and edible homologous traditional Chinese medicines (MEHTCMs), have been confirmed by a large number of studies to exert anti-inflammatory effects through multiple targets and are considered potential natural anti-inflammatory drugs. In addition, the structure of medical and edible homologous traditional Chinese medicines’ polysaccharides (MEHTCMPs) may be the key factor determining their anti-inflammatory activity, which makes the underlying the anti-inflammatory effects of polysaccharides and their structure–efficacy relationship hot topics of domestic and international research. However, due to the limitations of the current analytical techniques and tools, the structures have not been fully elucidated and the structure–efficacy relationship is relatively ambiguous, which are some of the difficulties in the process of developing and utilizing MEHTCMPs as novel anti-inflammatory drugs in the future. For this reason, this paper summarizes the potential anti-inflammatory mechanisms of MEHTCMPs, such as the regulation of the Toll-like receptor-related signaling pathway, MAPK signaling pathway, JAK-STAT signaling pathway, NLRP3 signaling pathway, PI3K-AKT signaling pathway, PPAR-γ signaling pathway, Nrf2-HO-1 signaling pathway, and the regulation of intestinal flora, and it systematically analyzes and evaluates the relationships between the anti-inflammatory activity of MEHTCMPs and their structures. Full article

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33 pages, 4277 KiB

Open AccessReview

Glycosylation Modulates the Structure and Functions of Collagen: A Review

by Igor Tvaroška

Molecules 2024, 29(7), 1417; https://doi.org/10.3390/molecules29071417 - 22 Mar 2024

Cited by 3 | Viewed by 5875

Abstract

Collagens are fundamental constituents of the extracellular matrix and are the most abundant proteins in mammals. Collagens belong to the family of fibrous or fiber-forming proteins that self-assemble into fibrils that define their mechanical properties and biological functions. Up to now, 28 members [...] Read more.

Collagens are fundamental constituents of the extracellular matrix and are the most abundant proteins in mammals. Collagens belong to the family of fibrous or fiber-forming proteins that self-assemble into fibrils that define their mechanical properties and biological functions. Up to now, 28 members of the collagen superfamily have been recognized. Collagen biosynthesis occurs in the endoplasmic reticulum, where specific post-translational modification—glycosylation—is also carried out. The glycosylation of collagens is very specific and adds β-d-galactopyranose and β-d-Glcp-(1→2)-d-Galp disaccharide through β-O-linkage to hydroxylysine. Several glycosyltransferases, namely COLGALT1, COLGALT2, LH3, and PGGHG glucosidase, were associated the with glycosylation of collagens, and recently, the crystal structure of LH3 has been solved. Although not fully understood, it is clear that the glycosylation of collagens influences collagen secretion and the alignment of collagen fibrils. A growing body of evidence also associates the glycosylation of collagen with its functions and various human diseases. Recent progress in understanding collagen glycosylation allows for the exploitation of its therapeutic potential and the discovery of new agents. This review will discuss the relevant contributions to understanding the glycosylation of collagens. Then, glycosyltransferases involved in collagen glycosylation, their structure, and catalytic mechanism will be surveyed. Furthermore, the involvement of glycosylation in collagen functions and collagen glycosylation-related diseases will be discussed. Full article

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13 pages, 15348 KiB

Open AccessArticle

Tailoring the Formation of Functionalized Furans from Glucose in Water with Nature-Sourced Catalysts and In Situ NMR

by Stefan S. Warthegau and Sebastian Meier

Molecules 2024, 29(6), 1368; https://doi.org/10.3390/molecules29061368 - 19 Mar 2024

Cited by 1 | Viewed by 1147

Abstract

Chain elongation of unprotected carbohydrates in water under mild conditions remains a challenge both in chemical and biochemical synthesis. The Knoevenagel addition or condensation enables transformations to bioactive scaffolds for pharmaceutical and agrochemical compounds. Unfortunately, the catalysts in use for these transformations often [...] Read more.

Chain elongation of unprotected carbohydrates in water under mild conditions remains a challenge both in chemical and biochemical synthesis. The Knoevenagel addition or condensation enables transformations to bioactive scaffolds for pharmaceutical and agrochemical compounds. Unfortunately, the catalysts in use for these transformations often reduce the green metrics of the transformations. Here, we use in situ NMR visualizations to explore the prospective use of natural catalysts for the synthesis of triple- and quadruple-functionalized furan- or dihydrofuran-derivatives from glucose and malononitrile. The dihydrofuran derivatives are formed as kinetic, major intermediates in the pathway to furan derivatives when using naturally abundant MgO or bio-sourced chitosan and N-Methyl-d-glucamine (meglumine) as the catalysts in water. Both catalyst loading, solvent composition and pH can be adapted to populate dihydrofurans with four substituents by slowing down their further reactions. Higher temperatures and higher pH values favor the formation of triple-functionalized furans over quadruple-substituted dihydrofurans, which may be bicyclic or monocyclic. Compared to more traditional catalysts, nature-sourced options offer more sustainable options that emulate natural processes. Visualization with in situ NMR contributes to streamlining the development of cheap and environmentally benign procedures for carbohydrate chain elongation. Full article

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16 pages, 7959 KiB

Open AccessArticle

Synthesis and Biological Evaluation of New Dihydrofuro[3,2-b]piperidine Derivatives as Potent α-Glucosidase Inhibitors

by Haibo Wang, Xiaojiang Huang, Yang Pan, Guoqing Zhang, Senling Tang, Huawu Shao and Wei Jiao

Molecules 2024, 29(5), 1179; https://doi.org/10.3390/molecules29051179 - 6 Mar 2024

Viewed by 1036

Abstract

Inhibition of glycoside hydrolases has widespread application in the treatment of diabetes. Based on our previous findings, a series of dihydrofuro[3,2-b]piperidine derivatives was designed and synthesized from D- and L-arabinose. Compounds 32 (IC₅₀ = 0.07 μM) and 28 (IC₅₀ [...] Read more.

Inhibition of glycoside hydrolases has widespread application in the treatment of diabetes. Based on our previous findings, a series of dihydrofuro[3,2-b]piperidine derivatives was designed and synthesized from D- and L-arabinose. Compounds 32 (IC₅₀ = 0.07 μM) and 28 (IC₅₀ = 0.5 μM) showed significantly stronger inhibitory potency against α-glucosidase than positive control acarbose. The study of the structure–activity relationship of these compounds provides a new clue for the development of new α-glucosidase inhibitors. Full article

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2023

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35 pages, 1808 KiB

Open AccessArticle

Innovative Metrics for Reporting and Comparing the Glycan Structural Profile in Biotherapeutics

by Renato Mastrangeli, Abhijeet Satwekar and Horst Bierau

Molecules 2023, 28(8), 3304; https://doi.org/10.3390/molecules28083304 - 7 Apr 2023

Cited by 2 | Viewed by 2654

Abstract

Glycosylation is a critical quality attribute in biotherapeutics, impacting properties such as protein stability, solubility, clearance rate, efficacy, immunogenicity, and safety. Due to the heterogenic and complex nature of protein glycosylation, comprehensive characterization is demanding. Moreover, the lack of standardized metrics for evaluating [...] Read more.

Glycosylation is a critical quality attribute in biotherapeutics, impacting properties such as protein stability, solubility, clearance rate, efficacy, immunogenicity, and safety. Due to the heterogenic and complex nature of protein glycosylation, comprehensive characterization is demanding. Moreover, the lack of standardized metrics for evaluating and comparing glycosylation profiles hinders comparability studies and the establishment of manufacturing control strategies. To address both challenges, we propose a standardized approach based on novel metrics for a comprehensive glycosylation fingerprint which greatly facilitates the reporting and objective comparison of glycosylation profiles. The analytical workflow is based on a liquid chromatography–mass spectrometry-based multi-attribute method. Based on the analytical data, a matrix of glycosylation-related quality attributes, both at site-specific and whole molecule level, are computed, which provide metrics for a comprehensive product glycosylation fingerprint. Two case studies illustrate the applicability of the proposed indices as a standardized and versatile approach for reporting all dimensions of the glycosylation profile. The proposed approach further facilitates the assessments of risks associated with changes in the glycosylation profile that may affect efficacy, clearance, and immunogenicity. Full article

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10 pages, 13392 KiB

Open AccessArticle

Expression and Characterisation of the First Snail-Derived UDP-Gal: Glycoprotein-N-acetylgalactosamine β-1,3-Galactosyltransferase (T-Synthase) from Biomphalaria glabrata

by Marilica Zemkollari, Markus Blaukopf, Reingard Grabherr and Erika Staudacher

Molecules 2023, 28(2), 552; https://doi.org/10.3390/molecules28020552 - 5 Jan 2023

Cited by 4 | Viewed by 2240

Abstract

UDP-Gal: glycoprotein-N-acetylgalactosamine β-1,3-galactosyltransferase (T-synthase, EC 2.4.1.122) catalyses the transfer of the monosaccharide galactose from UDP-Gal to GalNAc-Ser/Thr, synthesizing the core 1 mucin type O-glycan. Such glycans play important biological roles in a number of recognition processes. The crucial role of these glycans is [...] Read more.

UDP-Gal: glycoprotein-N-acetylgalactosamine β-1,3-galactosyltransferase (T-synthase, EC 2.4.1.122) catalyses the transfer of the monosaccharide galactose from UDP-Gal to GalNAc-Ser/Thr, synthesizing the core 1 mucin type O-glycan. Such glycans play important biological roles in a number of recognition processes. The crucial role of these glycans is acknowledged for mammals, but a lot remains unknown regarding invertebrate and especially mollusc O-glycosylation. Although core O-glycans have been found in snails, no core 1 β-1,3-galactosyltransferase has been described so far. Here, the sequence of the enzyme was identified by a BlastP search of the NCBI Biomphalaria glabrata database using the human T-synthase sequence (NP_064541.1) as a template. The obtained gene codes for a 388 amino acids long transmembrane protein with two putative N-glycosylation sites. The coding sequence was synthesised and expressed in Sf9 cells. The expression product of the putative enzyme displayed core 1 β-1,3-galactosyltransferase activity using pNP-α-GalNAc as the substrate. The enzyme showed some sequence homology (49.40% with Homo sapiens, 53.69% with Drosophila melanogaster and 49.14% with Caenorhabditis elegans) and similar biochemical parameters with previously characterized T-synthases from other phyla. In this study we present the identification, expression and characterisation of the UDP-Gal: glycoprotein-N-acetylgalactosamine β-1,3-galactosyltransferase from the fresh-water snail Biomphalaria glabrata, which is the first cloned T-synthase from mollusc origin. Full article

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2022

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18 pages, 3300 KiB

Open AccessArticle

Deacetylation and Desuccinylation of the Fucose-Rich Polysaccharide Fucopol: Impact on Biopolymer Physical and Chemical Properties

by Sílvia Baptista, Diana Araújo, Patrícia Concórdio-Reis, Ana C. Marques, Elvira Fortunato, Vítor D. Alves and Filomena Freitas

Molecules 2022, 27(21), 7165; https://doi.org/10.3390/molecules27217165 - 23 Oct 2022

Cited by 1 | Viewed by 2010

Abstract

FucoPol is an acylated polysaccharide with demonstrated valuable functional properties that include a shear thinning fluid behaviour, a film-forming capacity, and an emulsion forming and stabilizing capacity. In this study, the different conditions (concentration, temperature, and time) for alkaline treatment were investigated to [...] Read more.

FucoPol is an acylated polysaccharide with demonstrated valuable functional properties that include a shear thinning fluid behaviour, a film-forming capacity, and an emulsion forming and stabilizing capacity. In this study, the different conditions (concentration, temperature, and time) for alkaline treatment were investigated to deacylate FucoPol. Complete deacetylation and desuccinylation was achieved with 0.02 M NaOH, at 60 °C for 15 min, with no significant impact on the biopolymer’s sugar composition, pyruvate content, and molecular mass distribution. FucoPol depyruvylation by acid hydrolysis was attempted, but it resulted in a very low polymer recovery. The effect of the ionic strength, pH, and temperature on the deacetylated/desuccinylated polysaccharide, d-FucoPol, was evaluated, as well as its emulsion and film-forming capacity. d-FucoPol aqueous solutions maintained the shear thinning behaviour characteristic of FucoPol, but the apparent viscosity decreased significantly. Moreover, contrary to FucoPol, whose solutions were not affected by the media’s ionic strength, the d-FucoPol solutions had a significantly higher apparent viscosity for a higher ionic strength. On the other hand, the d-FucoPol solutions were not affected by the pH in the range of 3.6–11.5, while FucoPol had a decreased viscosity for acidic pH values and for a pH above 10.5. Although d-FucoPol displayed an emulsification activity for olive oil similar to that of FucoPol (98 ± 0%) for an oil-to-water ratio of 2:3, the emulsions were less viscous. The d-FucoPol films were flexible, with a higher Young′s modulus (798 ± 152 MPa), a stress at the break (22.5 ± 2.5 MPa), and an elongation at the break (9.3 ± 0.7%) than FucoPol (458 ± 32 MPa, 15.5 ± 0.3 MPa and 8.1 ± 1.0%, respectively). Given these findings, d-FucoPol arises as a promising novel biopolymer, with distinctive properties that may render it useful for utilization as a suspending or emulsifier agent, and as a barrier in coatings and packaging films. Full article

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18 pages, 1563 KiB

Open AccessArticle

A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease

by Alba L. Montoya, Elisa G. Carvajal, Uriel Ortega-Rodriguez, Igor L. Estevao, Roger A. Ashmus, Sohan R. Jankuru, Susana Portillo, Cameron C. Ellis, Colin D. Knight, Julio Alonso-Padilla, Luis Izquierdo, Maria-Jesus Pinazo, Joaquim Gascon, Veronica Suarez, Douglas M. Watts, Iliana R. Malo, Janine M. Ramsey, Belkisyolé Alarcón De Noya, Oscar Noya, Igor C. Almeida and Katja Michael Show full author list Hide full author list

Molecules 2022, 27(17), 5714; https://doi.org/10.3390/molecules27175714 - 5 Sep 2022

Cited by 3 | Viewed by 3178

Abstract

Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6–7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually [...] Read more.

Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6–7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose O-glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients. Full article

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2021

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17 pages, 24668 KiB

Open AccessArticle

HIV-1 Tat and Heparan Sulfate Proteoglycans Orchestrate the Setup of in Cis and in Trans Cell-Surface Interactions Functional to Lymphocyte Trans-Endothelial Migration

by Chiara Urbinati, Maria Milanesi, Nicola Lauro, Cinzia Bertelli, Guido David, Pasqualina D’Ursi, Marco Rusnati and Paola Chiodelli

Molecules 2021, 26(24), 7488; https://doi.org/10.3390/molecules26247488 - 10 Dec 2021

Cited by 7 | Viewed by 2963

Abstract

HIV-1 transactivating factor Tat is released by infected cells. Extracellular Tat homodimerizes and engages several receptors, including integrins, vascular endothelial growth factor receptor 2 (VEGFR2) and heparan sulfate proteoglycan (HSPG) syndecan-1 expressed on various cells. By means of experimental cell models recapitulating the [...] Read more.

HIV-1 transactivating factor Tat is released by infected cells. Extracellular Tat homodimerizes and engages several receptors, including integrins, vascular endothelial growth factor receptor 2 (VEGFR2) and heparan sulfate proteoglycan (HSPG) syndecan-1 expressed on various cells. By means of experimental cell models recapitulating the processes of lymphocyte trans-endothelial migration, here, we demonstrate that upon association with syndecan-1 expressed on lymphocytes, Tat triggers simultaneously the in cis activation of lymphocytes themselves and the in trans activation of endothelial cells (ECs). This “two-way” activation eventually induces lymphocyte adhesion and spreading onto the substrate and vascular endothelial (VE)-cadherin reorganization at the EC junctions, with consequent endothelial permeabilization, leading to an increased extravasation of Tat-presenting lymphocytes. By means of a panel of biochemical activation assays and specific synthetic inhibitors, we demonstrate that during the above-mentioned processes, syndecan-1, integrins, FAK, src and ERK_1/2 engagement and activation are needed in the lymphocytes, while VEGFR2, integrin, src and ERK_1/2 are needed in the endothelium. In conclusion, the Tat/syndecan-1 complex plays a central role in orchestrating the setup of the various in cis and in trans multimeric complexes at the EC/lymphocyte interface. Thus, by means of computational molecular modelling, docking and dynamics, we also provide a characterization at an atomic level of the binding modes of the Tat/heparin interaction, with heparin herein used as a structural analogue of the heparan sulfate chains of syndecan-1. Full article

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2020

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22 pages, 5552 KiB

Open AccessArticle

Specific Non-Reducing Ends in Heparins from Different Animal Origins: Building Blocks Analysis Using Reductive Amination Tagging by Sulfanilic Acid

by Pierre A. J. Mourier

Molecules 2020, 25(23), 5553; https://doi.org/10.3390/molecules25235553 - 26 Nov 2020

Cited by 8 | Viewed by 3032

Abstract

Heparins are linear sulfated polysaccharides widely used as anticoagulant drugs. Their nonreducing-end (NRE) has been little investigated due to challenges in their characterization, but is known to be partly generated by enzymatic cleavage with heparanases, resulting in N-sulfated glucosamines at the NRE. [...] Read more.

Heparins are linear sulfated polysaccharides widely used as anticoagulant drugs. Their nonreducing-end (NRE) has been little investigated due to challenges in their characterization, but is known to be partly generated by enzymatic cleavage with heparanases, resulting in N-sulfated glucosamines at the NRE. Uronic NRE (specifically glucuronic acids) have been isolated from porcine heparin, with GlcA-GlcNS,3S,6S identified as a porcine-specific NRE marker. To further characterize NRE in heparinoids, a building block analysis involving exhaustive heparinase digestion and subsequent reductive amination with sulfanilic acid was performed. This study describes a new method for identifying heparin classical building blocks and novel NRE building blocks using strong anion exchange chromatography on AS11 columns for the assay, and ion-pair liquid chromatography-mass spectrometry for building block identification. Porcine, ovine, and bovine intestine heparins were analyzed. Generally, NRE on these three heparins are highly sulfated moieties, particularly with 3-O sulfates, and the observed composition of the NRE is highly dependent on heparin origin. At the highest level of specificity, the isolated marker was only detected in porcine heparin. However, the proportion of glucosamines in the NRE and the proportion of glucuronic/iduronic configurations in the NRE uronic moieties greatly varied between heparin types. Full article

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2018

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11 pages, 1494 KiB

Open AccessTechnical Note

SugarSketcher: Quick and Intuitive Online Glycan Drawing

by Davide Alocci, Pavla Suchánková, Renaud Costa, Nicolas Hory, Julien Mariethoz, Radka Svobodová Vařeková, Philip Toukach and Frédérique Lisacek

Molecules 2018, 23(12), 3206; https://doi.org/10.3390/molecules23123206 - 5 Dec 2018

Cited by 14 | Viewed by 6526

Abstract

SugarSketcher is an intuitive and fast JavaScript interface module for online drawing of glycan structures in the popular Symbol Nomenclature for Glycans (SNFG) notation and exporting them to various commonly used formats encoding carbohydrate sequences (e.g., GlycoCT) or quality images (e.g., svg). It [...] Read more.

SugarSketcher is an intuitive and fast JavaScript interface module for online drawing of glycan structures in the popular Symbol Nomenclature for Glycans (SNFG) notation and exporting them to various commonly used formats encoding carbohydrate sequences (e.g., GlycoCT) or quality images (e.g., svg). It does not require a backend server or any specific browser plugins and can be integrated in any web glycoinformatics project. SugarSketcher allows drawing glycans both for glycobiologists and non-expert users. The “quick mode” allows a newcomer to build up a glycan structure having only a limited knowledge in carbohydrate chemistry. The “normal mode” integrates advanced options which enable glycobiologists to tailor complex carbohydrate structures. The source code is freely available on GitHub and glycoinformaticians are encouraged to participate in the development process while users are invited to test a prototype available on the ExPASY web-site and send feedback. Full article

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16 pages, 2269 KiB

Open AccessArticle

A Novel Integrated Way for Deciphering the Glycan Code for the FimH Lectin

by Tetiana Dumych, Clarisse Bridot, Sébastien G. Gouin, Marc F. Lensink, Solomiya Paryzhak, Sabine Szunerits, Ralf Blossey, Rostyslav Bilyy, Julie Bouckaert and Eva-Maria Krammer

Molecules 2018, 23(11), 2794; https://doi.org/10.3390/molecules23112794 - 28 Oct 2018

Cited by 13 | Viewed by 4334

Abstract

The fimbrial lectin FimH from uro- and enteropathogenic Escherichia coli binds with nanomolar affinity to oligomannose glycans exposing Manα1,3Man dimannosides at their non-reducing end, but only with micromolar affinities to Manα1,2Man dimannosides. These two dimannoses play a significantly distinct role in infection by [...] Read more.

The fimbrial lectin FimH from uro- and enteropathogenic Escherichia coli binds with nanomolar affinity to oligomannose glycans exposing Manα1,3Man dimannosides at their non-reducing end, but only with micromolar affinities to Manα1,2Man dimannosides. These two dimannoses play a significantly distinct role in infection by E. coli. Manα1,2Man has been described early on as shielding the (Manα1,3Man) glycan that is more relevant to strong bacterial adhesion and invasion. We quantified the binding of the two dimannoses (Manα1,2Man and Manα1,3Man to FimH using ELLSA and isothermal microcalorimetry and calculated probabilities of binding modes using molecular dynamics simulations. Our experimentally and computationally determined binding energies confirm a higher affinity of FimH towards the dimannose Manα1,3Man. Manα1,2Man displays a much lower binding enthalpy combined with a high entropic gain. Most remarkably, our molecular dynamics simulations indicate that Manα1,2Man cannot easily take its major conformer from water into the FimH binding site and that FimH is interacting with two very different conformers of Manα1,2Man that occupy 42% and 28% respectively of conformational space. The finding that Manα1,2Man binding to FimH is unstable agrees with the earlier suggestion that E. coli may use the Manα1,2Man epitope for transient tethering along cell surfaces in order to enhance dispersion of the infection. Full article

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17 pages, 1949 KiB

Open AccessReview

Applications of Ion Mobility-Mass Spectrometry in Carbohydrate Chemistry and Glycobiology

by Yuqing Mu, Benjamin L. Schulz and Vito Ferro

Molecules 2018, 23(10), 2557; https://doi.org/10.3390/molecules23102557 - 7 Oct 2018

Cited by 23 | Viewed by 4909

Abstract

Carbohydrate analyses are often challenging due to the structural complexity of these molecules, as well as the lack of suitable analytical tools for distinguishing the vast number of possible isomers. The coupled technique, ion mobility-mass spectrometry (IM-MS), has been in use for two [...] Read more.

Carbohydrate analyses are often challenging due to the structural complexity of these molecules, as well as the lack of suitable analytical tools for distinguishing the vast number of possible isomers. The coupled technique, ion mobility-mass spectrometry (IM-MS), has been in use for two decades for the analysis of complex biomolecules, and in recent years it has emerged as a powerful technique for the analysis of carbohydrates. For carbohydrates, most studies have focused on the separation and characterization of isomers in biological samples. IM-MS is capable of separating isomeric ions by drift time, and further characterizing them by mass analysis. Applications of IM-MS in carbohydrate analysis are extremely useful and important for understanding many biological mechanisms and for the determination of disease states, although efforts are still needed for higher sensitivity and resolution. Full article

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27 pages, 2488 KiB

Open AccessFeature PaperArticle

Synthesis and Preliminary Evaluation of Biological Activity of Glycoconjugates Analogues of Acyclic Uridine Derivatives

by Roman Komor, Gabriela Pastuch-Gawolek, Ewelina Krol and Wieslaw Szeja

Molecules 2018, 23(8), 2017; https://doi.org/10.3390/molecules23082017 - 13 Aug 2018

Cited by 4 | Viewed by 3833

Abstract

Herein we present the methodology for obtaining glycosyltransferase inhibitors, analogues of natural enzyme substrates of donor-type: UDP-glucose and UDP-galactose. The synthesis concerned glycoconjugates, nucleoside analogues containing an acyclic ribose mimetic linked to a uracil moiety in their structure. The biological activity of the [...] Read more.

Herein we present the methodology for obtaining glycosyltransferase inhibitors, analogues of natural enzyme substrates of donor-type: UDP-glucose and UDP-galactose. The synthesis concerned glycoconjugates, nucleoside analogues containing an acyclic ribose mimetic linked to a uracil moiety in their structure. The biological activity of the synthesised compounds was determined on the basis of their ability to inhibit the model enzyme action of β-1,4-galactosyltransferase from bovine milk. The obtained results allowed to expand and supplement the existing library of synthetic compounds that are able to regulate the biological activity of enzymes from the GT class. Full article

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24 pages, 6763 KiB

Open AccessArticle

Novel Uridine Glycoconjugates, Derivatives of 4-Aminophenyl 1-Thioglycosides, as Potential Antiviral Compounds

by Ewelina Krol, Gabriela Pastuch-Gawolek, Binay Chaubey, Gabriela Brzuska, Karol Erfurt and Boguslaw Szewczyk

Molecules 2018, 23(6), 1435; https://doi.org/10.3390/molecules23061435 - 13 Jun 2018

Cited by 3 | Viewed by 4123

Abstract

A novel series of uridine glycoconjugates, derivatives of 4-aminophenyl 1-thioglycosides, was designed and synthesized. All compounds were evaluated in vitro for their antiviral activity against hepatitis C virus (HCV) and classical swine fever virus (CSFV), two important human and animal viral pathogens for [...] Read more.

A novel series of uridine glycoconjugates, derivatives of 4-aminophenyl 1-thioglycosides, was designed and synthesized. All compounds were evaluated in vitro for their antiviral activity against hepatitis C virus (HCV) and classical swine fever virus (CSFV), two important human and animal viral pathogens for which new or improved therapeutic options are needed. The antiviral activity of all synthesized compounds was confirmed using pseudo-plaque reduction assays in which a significant arrest of CSFV and HCV growth was observed in the presence of these compounds. Two of the synthesized compounds, 9 and 12, displayed a significant inhibitory effect on HCV and CSFV propagation with IC₅₀ values of 4.9 and 13.5 µM for HCV and 4.2 and 4 µM for CSFV, respectively, with low cytotoxicity. Using various infection and replication models, we have shown that both compounds were able to significantly reduce viral genome replication by up to 90% with IC₅₀ values in the low micromolar range. A structure activity analysis of the synthesized compounds showed that the high antiviral activity was attributed to the hydrophobicity of glycoconjugates and the introduction of elements capable to coordinate metal ions into the spacer connecting the sugar and uridine moiety, which can be useful in the development of new antiviral compounds in the future. Full article

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2016

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1951 KiB

Open AccessArticle

Investigating Glycol-Split-Heparin-Derived Inhibitors of Heparanase: A Study of Synthetic Trisaccharides

by Minghong Ni, Stefano Elli, Annamaria Naggi, Marco Guerrini, Giangiacomo Torri and Maurice Petitou

Molecules 2016, 21(11), 1602; https://doi.org/10.3390/molecules21111602 - 23 Nov 2016

Cited by 17 | Viewed by 6034

Abstract

Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their [...] Read more.

Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their strong inhibitory activity. We describe here the total chemical synthesis of the trisaccharide GlcNS6S-GlcA-1,6anGlcNS (1) and its glycol-split (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS (2) from glucose. As expected, in a heparanase inhibition assay, compound 2 is one order of magnitude more potent than 1. Using molecular modeling techniques we have created a 3D model of 1 and 2 that has been validated by NOESY NMR experiments. The pure synthetic oligosaccharides have allowed the first in depth study of the conformation of a glycol-split glucuronic acid. Introducing a glycol-split unit in the structure of 1 increases the conformational flexibility and shortens the distance between the two glucosamine motives, thus promoting interaction with heparanase. However, comparing the relative activities of 2 and roneparstat, we can conclude that the glycol-split motive is not the only determinant of the strong inhibitory effect of roneparstat. Full article

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12236 KiB

Open AccessReview

Influenza Neuraminidase Inhibitors: Synthetic Approaches, Derivatives and Biological Activity

by Pedro Laborda, Su-Yan Wang and Josef Voglmeir

Molecules 2016, 21(11), 1513; https://doi.org/10.3390/molecules21111513 - 11 Nov 2016

Cited by 64 | Viewed by 21795

Abstract

Despite being a common viral disease, influenza has very negative consequences, causing the death of around half a million people each year. A neuraminidase located on the surface of the virus plays an important role in viral reproduction by contributing to the release [...] Read more.

Despite being a common viral disease, influenza has very negative consequences, causing the death of around half a million people each year. A neuraminidase located on the surface of the virus plays an important role in viral reproduction by contributing to the release of viruses from infected host cells. The treatment of influenza is mainly based on the administration of neuraminidase inhibitors. The neuraminidase inhibitors zanamivir, laninamivir, oseltamivir and peramivir have been commercialized and have been demonstrated to be potent influenza viral neuraminidase inhibitors against most influenza strains. In order to create more potent neuraminidase inhibitors and fight against the surge in resistance resulting from naturally-occurring mutations, these anti-influenza drugs have been used as templates for the development of new neuraminidase inhibitors through structure-activity relationship studies. Here, we review the synthetic routes to these commercial drugs, the modifications which have been performed on these structures and the effects of these modifications on their inhibitory activity. Full article

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1267 KiB

Open AccessArticle

A Modular Synthetic Approach to Isosteric Sulfonic Acid Analogues of the Anticoagulant Pentasaccharide Idraparinux

by Erika Mező, Dániel Eszenyi, Eszter Varga, Mihály Herczeg and Anikó Borbás

Molecules 2016, 21(11), 1497; https://doi.org/10.3390/molecules21111497 - 11 Nov 2016

Cited by 6 | Viewed by 5528

Abstract

Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we [...] Read more.

Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we elaborated a modular pathway to obtain a series of idraparinux-analogue pentasaccharides bearing one or two primary sulfonic acid moieties. Five protected pentasaccharides with different C-sulfonation patterns were prepared by two subsequent glycosylation reactions, respectively, using two monosaccharide and four disaccharide building blocks. Transformation of the protected derivatives into the fully O-sulfated, O-methylated sulfonic acid end-products was also studied. Full article

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Open AccessArticle

Agavins Increase Neurotrophic Factors and Decrease Oxidative Stress in the Brains of High-Fat Diet-Induced Obese Mice

by Elena Franco-Robles and Mercedes G. López

Molecules 2016, 21(8), 998; https://doi.org/10.3390/molecules21080998 - 2 Aug 2016

Cited by 36 | Viewed by 9560

Abstract

Background: Fructans obtained from agave, called agavins, have recently shown significant benefits for human health including obesity. Therefore, we evaluated the potential of agavins as neuroprotectors and antioxidants by determining their effect on brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) as [...] Read more.

Background: Fructans obtained from agave, called agavins, have recently shown significant benefits for human health including obesity. Therefore, we evaluated the potential of agavins as neuroprotectors and antioxidants by determining their effect on brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) as well as oxidative brain damage in of obese mice. Methods: Male C57BL/6J mice were fed a high-fat diet (HFD) and treated daily with 5% (HFD/A5) or 10% (HFD/A10) of agavins or a standard diet (SD) for 10 weeks. The levels of BDNF and GDNF were evaluated by ELISA. The oxidative stress was evaluated by lipid peroxidation (TBARS) and carbonyls. SCFAs were also measured with GC-FID. Differences between groups were assessed using ANOVA and by Tukey’s test considering p < 0.05. Results: The body weight gain and food intake of mice HFD/A10 group were significantly lower than those in the HFD group. Agavins restored BDNF levels in HFD/A5 group and GDNF levels of HFD/A5 and HFD/A10 groups in cerebellum. Interestingly, agavins decreased TBARS levels in HFD/A5 and HFD/A10 groups in the hippocampus, frontal cortex and cerebellum. Carbonyl levels were also lower in HFD/A5 and HFD/A10 for only the hippocampus and cerebellum. It was also found that agavins enhanced SCFAs production in feces. Conclusion: Agavins may act as bioactive ingredients with antioxidant and protective roles in the brain. Full article

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11736 KiB

Open AccessReview

Multivalent Carbohydrate-Lectin Interactions: How Synthetic Chemistry Enables Insights into Nanometric Recognition

by René Roy, Paul V. Murphy and Hans-Joachim Gabius

Molecules 2016, 21(5), 629; https://doi.org/10.3390/molecules21050629 - 13 May 2016

Cited by 59 | Viewed by 11770

Abstract

Glycan recognition by sugar receptors (lectins) is intimately involved in many aspects of cell physiology. However, the factors explaining the exquisite selectivity of their functional pairing are not yet fully understood. Studies toward this aim will also help appraise the potential for lectin-directed [...] Read more.

Glycan recognition by sugar receptors (lectins) is intimately involved in many aspects of cell physiology. However, the factors explaining the exquisite selectivity of their functional pairing are not yet fully understood. Studies toward this aim will also help appraise the potential for lectin-directed drug design. With the network of adhesion/growth-regulatory galectins as therapeutic targets, the strategy to recruit synthetic chemistry to systematically elucidate structure-activity relationships is outlined, from monovalent compounds to glyco-clusters and glycodendrimers to biomimetic surfaces. The versatility of the synthetic procedures enables to take examining structural and spatial parameters, alone and in combination, to its limits, for example with the aim to produce inhibitors for distinct galectin(s) that exhibit minimal reactivity to other members of this group. Shaping spatial architectures similar to glycoconjugate aggregates, microdomains or vesicles provides attractive tools to disclose the often still hidden significance of nanometric aspects of the different modes of lectin design (sequence divergence at the lectin site, differences of spatial type of lectin-site presentation). Of note, testing the effectors alone or in combination simulating (patho)physiological conditions, is sure to bring about new insights into the cooperation between lectins and the regulation of their activity. Full article

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Open AccessArticle

Efficient Synthesis of the Lewis A Tandem Repeat

by Daisuke Kobayashi, Akiharu Ueki, Tomoya Yamaji, Kazuya Nagao, Akihiro Imamura, Hiromune Ando, Makoto Kiso and Hideharu Ishida

Molecules 2016, 21(5), 614; https://doi.org/10.3390/molecules21050614 - 11 May 2016

Cited by 5 | Viewed by 5845

Abstract

The convergent synthesis of the Lewis A (Le^a) tandem repeat is described. The Le^a tandem repeat is a carbohydrate ligand for a mannose binding protein that shows potent inhibitory activity against carcinoma growth. The Le^a unit, {β-d-Gal-(1→3)-[α- [...] Read more.

The convergent synthesis of the Lewis A (Le^a) tandem repeat is described. The Le^a tandem repeat is a carbohydrate ligand for a mannose binding protein that shows potent inhibitory activity against carcinoma growth. The Le^a unit, {β-d-Gal-(1→3)-[α-l-Fuc-(1→4)]-β-d-GlcNAc}, was synthesized by stereoselective nitrile-assisted β-galactosylation with the phenyl 3-O-allyl-2,4,6-tri-O-benzyl-1-thio-β-galactoside, and ether-assisted α-fucosylation with fucosyl (N-phenyl)trifluoroacetimidate. This common Le^a unit was easily converted to an acceptor and donor in high yields, and the stereoselective assembly of the hexasaccharide and dodecasaccharide as the Le^a tandem repeat framework was achieved by 2-trichloroacetamido-assisted β-glycosylation and the (N-phenyl)trifluoroacetimidate method. Full article

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Open AccessReview

Polysaccharides from the Marine Environment with Pharmacological, Cosmeceutical and Nutraceutical Potential

by Nadia Ruocco, Susan Costantini, Stefano Guariniello and Maria Costantini

Molecules 2016, 21(5), 551; https://doi.org/10.3390/molecules21050551 - 27 Apr 2016

Cited by 200 | Viewed by 16113

Abstract

Carbohydrates, also called saccharides, are molecules composed of carbon, hydrogen, and oxygen. They are the most abundant biomolecules and essential components of many natural products and have attracted the attention of researchers because of their numerous human health benefits. Among carbohydrates the polysaccharides [...] Read more.

Carbohydrates, also called saccharides, are molecules composed of carbon, hydrogen, and oxygen. They are the most abundant biomolecules and essential components of many natural products and have attracted the attention of researchers because of their numerous human health benefits. Among carbohydrates the polysaccharides represent some of the most abundant bioactive substances in marine organisms. In fact, many marine macro- and microorganisms are good resources of carbohydrates with diverse applications due to their biofunctional properties. By acting on cell proliferation and cycle, and by modulating different metabolic pathways, marine polysaccharides (including mainly chitin, chitosan, fucoidan, carrageenan and alginate) also have numerous pharmaceutical activities, such as antioxidative, antibacterial, antiviral, immuno-stimulatory, anticoagulant and anticancer effects. Moreover, these polysaccharides have many general beneficial effects for human health, and have therefore been developed into potential cosmeceuticals and nutraceuticals. In this review we describe current advances in the development of marine polysaccharides for nutraceutical, cosmeceutical and pharmacological applications. Research in this field is opening new doors for harnessing the potential of marine natural products. Full article

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2015

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3093 KiB

Open AccessArticle

An Unusual Carbohydrate Conformation is Evident in Moraxella catarrhalis Oligosaccharides

by Martin Frank, Patrick M. Collins, Ian R. Peak, I. Darren Grice and Jennifer C. Wilson

Molecules 2015, 20(8), 14234-14253; https://doi.org/10.3390/molecules200814234 - 5 Aug 2015

Cited by 11 | Viewed by 6835

Abstract

Oligosaccharide structures derived from the lipooligosaccharide of M. catarrhalis show that the highly branched glucose-rich inner core of the oligosaccharide has an altered conformation compared to the most truncated tetra-glucose-Kdo lgt1/4Δ oligosaccharide structure. Addition of one residue each to the (1-4) and (1-6) [...] Read more.

Oligosaccharide structures derived from the lipooligosaccharide of M. catarrhalis show that the highly branched glucose-rich inner core of the oligosaccharide has an altered conformation compared to the most truncated tetra-glucose-Kdo lgt1/4Δ oligosaccharide structure. Addition of one residue each to the (1-4) and (1-6) chains to give the lgt2Δ oligosaccharide is the minimum requirement for this conformational change to occur. Extensive molecular modeling and NMR investigations have shown that the (1-3), (1-4), and (1-6) glycosidic linkages from the central α-D-Glcp have significantly altered conformational preferences between the two structures. For the lgt1/4Δ oligosaccharide the (1-3) and (1-4) linkage populates predominantly the syn minimum on the conformational free energy map and for the (1-6) linkage conformational flexibility is observed, which is supported by ¹H-NMR T1 measurements. For the lgt2Δ oligosaccharide the unusual “(1-4)anti-ψ(1-6)gg” conformation, which could be confirmed by long-range NOE signals, is a dominant conformation in which the oligosaccharide is very compact with the terminal α-D-GlcNAc residue folding back towards the center of the molecule leading to an extensive intra-molecular hydrophobic interaction between the terminal residues. Comparing effective H-H distances, which were calculated for conformational sub-ensembles, with the NOE distances revealed that typically multiple conformations could be present without significantly violating the measured NOE restraints. For lgt2Δ the presence of more than one conformation is supported by the NOE data. Full article

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993 KiB

Open AccessReview

A Survey of Recent Synthetic Applications of 2,3-Dideoxy-Hex-2-enopyranosides

by Ana M. Gomez, Fernando Lobo, Silvia Miranda and J. Cristobal Lopez

Molecules 2015, 20(5), 8357-8394; https://doi.org/10.3390/molecules20058357 - 8 May 2015

Cited by 20 | Viewed by 9904

Abstract

Unsaturated carbohydrate derivatives are useful intermediates in synthetic transformations leading to a variety of compounds. The aim of this review is to highlight the rich chemistry of ∆-2,3 unsaturated pyranosides, emphasizing the variety of transformations that have been carried out in these substrates [...] Read more.

Unsaturated carbohydrate derivatives are useful intermediates in synthetic transformations leading to a variety of compounds. The aim of this review is to highlight the rich chemistry of ∆-2,3 unsaturated pyranosides, emphasizing the variety of transformations that have been carried out in these substrates during the last decade. Full article

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3807 KiB

Open AccessArticle

Accumulation of G_D1α Ganglioside in MDA-MB-231 Breast Cancer Cells Expressing ST6GalNAc V

by Sandy Vandermeersch, Jorick Vanbeselaere, Clément P. Delannoy, Aurore Drolez, Caroline Mysiorek, Yann Guérardel, Philippe Delannoy and Sylvain Julien

Molecules 2015, 20(4), 6913-6924; https://doi.org/10.3390/molecules20046913 - 16 Apr 2015

Cited by 19 | Viewed by 6868

Abstract

α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for G_M1b [...] Read more.

α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for G_M1b, to form G_D1α and is considered as the main enzyme involved in the biosynthesis of α-series gangliosides. Recently, ST6GALNAC5 was identified as one of the genes over-expressed in breast cancer cell populations selected for their ability to produce brain metastasis. However, the capacity of human breast cancer cells to produce α-series gangliosides has never been clearly demonstrated. Here, we show by stable transfection and MS-MS analysis of total glycosphingolipids that ST6GALNAC5 expressing MDA-MB-231 breast cancer cells accumulate G_D1_α ganglioside (IV³Neu5Ac₁, III⁶Neu5Ac₁Gg₄-Cer). Full article

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851 KiB

Open AccessArticle

Characterization at 25 °C of Sodium Hyaluronate in Aqueous Solutions Obtained by Transport Techniques

by Aleš Mráček, Lenka Gřundělová, Antonín Minařík, Luís M. P. Veríssimo, Marisa C. F. Barros and Ana C. F. Ribeiro

Molecules 2015, 20(4), 5812-5824; https://doi.org/10.3390/molecules20045812 - 2 Apr 2015

Cited by 6 | Viewed by 6702

Abstract

Mutual diffusion coefficients, D, were determined for aqueous solutions of sodium hyaluronate (NaHy) at 25 °C and concentrations ranging from 0.00 to 1.00 g·dm⁻³ using the Taylor dispersion technique. From these experimental data, it was possible to estimate some parameters, such [...] Read more.

Mutual diffusion coefficients, D, were determined for aqueous solutions of sodium hyaluronate (NaHy) at 25 °C and concentrations ranging from 0.00 to 1.00 g·dm⁻³ using the Taylor dispersion technique. From these experimental data, it was possible to estimate some parameters, such as the hydrodynamic radius R_h, and the diffusion coefficient at infinitesimal concentration, D⁰, of hyaluronate ion, permitting us to have a better understanding of the structure of these systems of sodium hyaluronate in aqueous solutions. The additional viscosity measurements were done and Huggins constant, k_H, and limiting viscosity number, [η], were computed for interaction NaHy/water and NaHy/NaHy determination. Full article

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Open AccessArticle

Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

by Denong Wang, Jin Tang, Jiulai Tang and Lai-Xi Wang

Molecules 2015, 20(3), 4610-4622; https://doi.org/10.3390/molecules20034610 - 12 Mar 2015

Cited by 8 | Viewed by 10783

Abstract

Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for [...] Read more.

Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV), and human cytomegalovirus (HCMV). In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man₉GlcNAc₂Asn (Man9)-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn). These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation. Full article

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Open AccessArticle

Purification and Characterization of Chitinases from Ridgetail White Prawn Exopalaemon carinicauda

by Jing Wang, Jiquan Zhang, Fengge Song, Tianshu Gui and Jianhai Xiang

Molecules 2015, 20(2), 1955-1967; https://doi.org/10.3390/molecules20021955 - 26 Jan 2015

Cited by 28 | Viewed by 8000

Abstract

In this paper, we purified two native chitinases from the hepatopancreas of the ridgetail white prawn Exopalaemon carinicauda by using ion-exchange resin chromatography (IEC) and gel filtration. These two chitinases, named EcChi1 and EcChi2, were identified by chitinolytic activity assay and LC-ESI-MS/MS. Their [...] Read more.

In this paper, we purified two native chitinases from the hepatopancreas of the ridgetail white prawn Exopalaemon carinicauda by using ion-exchange resin chromatography (IEC) and gel filtration. These two chitinases, named EcChi1 and EcChi2, were identified by chitinolytic activity assay and LC-ESI-MS/MS. Their apparent molecular weights were 44 kDa and 65 kDa as determined by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The specific activity of EcChi1 and EcChi2 was 1305.97 U·mg⁻¹ and 28.69 U·mg⁻¹. The optimal temperature and pH of EcChi1 were 37 °C and pH 4.0, respectively. Co²⁺, Fe³⁺, Zn²⁺, Cd²⁺, and Cu²⁺ had an obvious promoting effect upon chitinase activity of EcChi1. For colloidal chitin, the K_m and V_max values of EcChi1 were 2.09 mg·mL⁻¹ and 31.15 U·mL⁻¹·h⁻¹. Full article

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2014

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Open AccessArticle

Profiling of Concanavalin A-Binding Glycoproteins in Human Hepatic Stellate Cells Activated with Transforming Growth Factor-β1

by Yannan Qin, Yaogang Zhong, Ganglong Yang, Tianran Ma, Liyuan Jia, Chen Huang and Zheng Li

Molecules 2014, 19(12), 19845-19867; https://doi.org/10.3390/molecules191219845 - 28 Nov 2014

Cited by 16 | Viewed by 9658

Abstract

Glycoproteins play important roles in maintaining normal cell functions depending on their glycosylations. Our previous study indicated that the abundance of glycoproteins recognized by concanavalin A (ConA) was increased in human hepatic stellate cells (HSCs) following activation by transforming growth factor-β1 (TGF-β1); however, [...] Read more.

Glycoproteins play important roles in maintaining normal cell functions depending on their glycosylations. Our previous study indicated that the abundance of glycoproteins recognized by concanavalin A (ConA) was increased in human hepatic stellate cells (HSCs) following activation by transforming growth factor-β1 (TGF-β1); however, little is known about the ConA-binding glycoproteins (CBGs) of HSCs. In this study, we employed a targeted glycoproteomics approach using lectin-magnetic particle conjugate-based liquid chromatography-tandem mass spectrometry to compare CBG profiles between LX-2 HSCs with and without activation by TGF-β1, with the aim of discovering novel CBGs and determining their possible roles in activated HSCs. A total of 54 and 77 proteins were identified in the quiescent and activated LX-2 cells, respectively. Of the proteins identified, 14.3% were glycoproteins and 73.3% were novel potential glycoproteins. Molecules involved in protein processing in the endoplasmic reticulum (e.g., calreticulin) and calcium signaling (e.g., 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase β-2 [PLCB2]) were specifically identified in activated LX-2 cells. Additionally, PLCB2 expression was upregulated in the cytoplasm of the activated LX-2 cells, as well as in the hepatocytes and sinusoidal cells of liver cirrhosis tissues. In conclusion, the results of this study may aid future investigations to find new molecular mechanisms involved in HSC activation and antifibrotic therapeutic targets. Full article

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2013

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545 KiB

Open AccessArticle

Artificial and Natural Sialic Acid Precursors Influence the Angiogenic Capacity of Human Umbilical Vein Endothelial Cells

by Nils B. Bayer, Uwe Schubert, Zehra Sentürk, Silvia Rudloff, Sandra Frank, Heike Hausmann, Hildegard Geyer, Rudolf Geyer, Klaus T. Preissner and Sebastian P. Galuska

Molecules 2013, 18(3), 2571-2586; https://doi.org/10.3390/molecules18032571 - 26 Feb 2013

Cited by 16 | Viewed by 9652

Abstract

N-acetylneuraminic acid (Neu5Ac) represents the most common terminal carbohydrate residue in many mammalian glycoconjugates and is directly involved in a number of different physiological as well as pathological cellular processes. Endogenous sialic acids derive from the biosynthetic precursor molecule N-acetyl-D-mannosamine (ManNAc). [...] Read more.

N-acetylneuraminic acid (Neu5Ac) represents the most common terminal carbohydrate residue in many mammalian glycoconjugates and is directly involved in a number of different physiological as well as pathological cellular processes. Endogenous sialic acids derive from the biosynthetic precursor molecule N-acetyl-D-mannosamine (ManNAc). Interestingly, N-acyl-analogues of D-mannosamine (ManN) can also be incorporated and converted into corresponding artificial sialic acids by eukaryotic cells. Within this study, we optimized a protocol for the chemical synthesis of various peracetylated ManN derivatives resulting in yields of approximately 100%. Correct molecular structures of the obtained products ManNAc, N-propanoyl-ManN (ManNProp) and N-butyl-ManN (ManNBut) were verified by GC-, ESI-MS- and NMR-analyses. By applying these substances to human umbilical vein endothelial cells (HUVECs), we could show that each derivative was metabolized to the corresponding N-acylneuraminic acid variant and subsequently incorporated into nascent glycoproteins. To investigate whether natural and/or artificial sialic acid precursors are able to modulate the angiogenic capacity of HUVECs, a spheroid assay was performed. By this means, an increase in total capillary length has been observed when cells incorporated N-butylneuraminic acid (Neu5But) into their glycoconjugates. In contrast, the natural precursor ManNAc inhibited the growth of capillaries. Thus, sialic acid precursors may represent useful agents to modulate blood vessel formation. Full article

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989 KiB

Open AccessReview

Chemistry and Applications of Polysaccharide Solutions in Strong Electrolytes/Dipolar Aprotic Solvents: An Overview

by Omar A. El Seoud, Haq Nawaz and Elizabeth P. G. Arêas

Molecules 2013, 18(1), 1270-1313; https://doi.org/10.3390/molecules18011270 - 21 Jan 2013

Cited by 53 | Viewed by 9511

Abstract

Biopolymers and their derivatives are being actively investigated as substitutes for petroleum-based polymers. This has generated an intense interest in investigating new solvents, in particular for cellulose, chitin/chitosan, and starch. This overview focuses on recent advances in the dissolution and derivatization of these [...] Read more.

Biopolymers and their derivatives are being actively investigated as substitutes for petroleum-based polymers. This has generated an intense interest in investigating new solvents, in particular for cellulose, chitin/chitosan, and starch. This overview focuses on recent advances in the dissolution and derivatization of these polysaccharides in solutions of strong electrolytes in dipolar aprotic solvents. A brief description of the molecular structures of these biopolymers is given, with emphases on the properties that are relevant to derivatization, namely crystallinity and accessibility. The mechanism of cellulose dissolution is then discussed, followed by a description of the strategies employed for the synthesis of cellulose derivatives (carboxylic acid esters, and ethers) under homogeneous reaction conditions. The same sequence of presentation has been followed for chitin/chitosan and starch. Future perspectives for this subject are summarized, in particular with regard to compliance with the principles of green chemistry. Full article

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2012

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936 KiB

Open AccessArticle

The Binding Affinity and Molecular Basis of the Structure-Binding Relationship between Urinary Tamm-Horsfall Glycoprotein and Tumor Necrosis Factor-α

by Cheng-Han Wu, Ko-Jen Li, Sue-Cien Siao, Yu-Hsuan Chen, Tsai-Hung Wu, Chang-Youh Tsai and Chia-Li Yu

Molecules 2012, 17(10), 11978-11989; https://doi.org/10.3390/molecules171011978 - 11 Oct 2012

Cited by 9 | Viewed by 7326

Abstract

In a previous study we noted significant THP binding to TNF-α, but did not explore the molecular basis of the structure-binding relationship. In this study, we used lectin-binding ELISA to assess the carbohydrate compositions of THP, BSA, IgG, TNF-α, and IFN-g. We identified [...] Read more.

In a previous study we noted significant THP binding to TNF-α, but did not explore the molecular basis of the structure-binding relationship. In this study, we used lectin-binding ELISA to assess the carbohydrate compositions of THP, BSA, IgG, TNF-α, and IFN-g. We identified β(1,4)-N-acetylglucosamine oligomers (GlcNAc) and GlcNAc/branched mannose in BSA, IgG, TNF-α, and THP, but not in IFN-g. These carbohydrate moieties mediated binding with THP. Small amounts of Siaα(2,3)Gal/ GalNAc, Sia(2,6)Gal/GalNAc, and mannose residues were also present in THP and TNF-α. Binding affinity (K_d) between THP and TNF-α by Scatchard plot analysis was 1.4–1.7 × 10⁻⁶ M, lower than antigen-antibody or ligand-receptor binding affinities. To elucidate the structure-binding relationship of THP-TNF-α, THP was digested with neuraminidase, β-galactosidase, O-sialoglycoprotein endopeptidase, carboxypeptidase Y, or proteinase K. β-galactosidase increased binding capacity of THP for TNF-α. Monosaccharide inhibition suggested that α-methyl-D-mannoside, GlcNAc, and GalNAc, but not sialic acid, suppress THP-TNF-α binding as detected by ELISA. We conclude that sugar-lectin and sugar-protein interactions between cognate sites in THP and TNF-α mediate their binding. Full article

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839 KiB

Open AccessArticle

Syntheses of Sulfo-Glycodendrimers Using Click Chemistry and Their Biological Evaluation

by Yoshiko Miura, Shunsuke Onogi and Tomohiro Fukuda

Molecules 2012, 17(10), 11877-11896; https://doi.org/10.3390/molecules171011877 - 9 Oct 2012

Cited by 15 | Viewed by 8422

Abstract

A series of novel glycol-clusters containing sulfonated N-acetyl-D-glucosamine (GlcNAc) have been synthesized using click chemistry. Three dendrimers with aromatic dendrons were synthesized using chlorination, azidation and click chemistries. The resulting dendrimers were modified with azide-terminated sulfonated GlcNAc using click chemistry. The sulfonated [...] Read more.

A series of novel glycol-clusters containing sulfonated N-acetyl-D-glucosamine (GlcNAc) have been synthesized using click chemistry. Three dendrimers with aromatic dendrons were synthesized using chlorination, azidation and click chemistries. The resulting dendrimers were modified with azide-terminated sulfonated GlcNAc using click chemistry. The sulfonated dendrimers showed affinity for proteins, including the lectin wheat germ agglutinin and amyloid beta peptide (1-42). The dendrimers of G1 and G2 in particular showed the largest affinity for the proteins. The addition of the sulfonated GlcNAc dendrimers of G1 and G2 exhibited an inhibition effect on the aggregation of the amyloid beta peptide, reduced the b-sheet conformation, and led to a reduction in the level of nanofiber formation. Full article

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288 KiB

Open AccessArticle

A Concise Synthesis of Glycolipids Based on Aspartic Acid Building Blocks

by Trinidad Velasco-Torrijos, Lorna Abbey and Roisin O’Flaherty

Molecules 2012, 17(10), 11346-11362; https://doi.org/10.3390/molecules171011346 - 25 Sep 2012

Cited by 3 | Viewed by 8159

Abstract

L-Aspartic acid building blocks bearing galactosyl moieties were used to synthesise glycolipid mimetics of variable hydrocarbon chain length. The glycolipids were readily prepared through amide bond formation using the TBTU/HOBt coupling methodology. It was observed that, under these conditions, activation of the α-carboxylic [...] Read more.

L-Aspartic acid building blocks bearing galactosyl moieties were used to synthesise glycolipid mimetics of variable hydrocarbon chain length. The glycolipids were readily prepared through amide bond formation using the TBTU/HOBt coupling methodology. It was observed that, under these conditions, activation of the α-carboxylic acid of the intermediates led to near complete racemisation of the chiral centre if the reaction was carried out in the presence of a base such as triethylamine. The enantiomerically pure glycolipids were obtained after careful consideration of the synthetic sequence and by performing the coupling reactions in the absence of base. Full article

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211 KiB

Open AccessCommunication

Inhibition of Burkholderia multivorans Adhesion to Lung Epithelial Cells by Bivalent Lactosides

by Ciara Wright, Rosaria Leyden, Paul V. Murphy, Máire Callaghan, Trinidad Velasco-Torrijos and Siobhán McClean

Molecules 2012, 17(9), 10065-10071; https://doi.org/10.3390/molecules170910065 - 24 Aug 2012

Cited by 2 | Viewed by 5571

Abstract

Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in cystic fibrosis patients which is inherently resistant to antimicrobial agents. The mechanisms of attachment and pathogenesis of Bcc, a group of 17 species, are poorly understood. The most commonly identified Bcc species in newly [...] Read more.

Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in cystic fibrosis patients which is inherently resistant to antimicrobial agents. The mechanisms of attachment and pathogenesis of Bcc, a group of 17 species, are poorly understood. The most commonly identified Bcc species in newly colonised patients, Burkholderia multivorans, continues to be acquired from the environment. Development of therapies which can prevent or reduce the risk of colonization on exposure to Bcc in the environment would be a better alternative to antimicrobial agents. Previously, it has been shown that Bcc strains bound to many glycolipid receptors on lung epithelia. Using a real-time PCR method to quantify the levels of binding of B. multivorans to the lung epithelial cells, we have examined glycoconjugate derivatives for their potential to inhibit host cell attachment. Bivalent lactosides previously shown to inhibit galectin binding significantly reduced the attachment of B. multivorans to CF lung epithelial cells at micromolar concentrations. This was in contrast to monosaccharides and lactose, which were only effective in the millimolar range. Development of glycoconjugate therapies such as these, which inhibit attachment to lung epithelial cells, represent an alternative means of preventing infection with inherently antimicrobially resistant pathogens such as B. multivorans. Full article

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416 KiB

Open AccessArticle

Anti-metastatic Semi-synthetic Sulfated Maltotriose C-C Linked Dimers. Synthesis and Characterisation

by Elena Vismara, Alessia Coletti, Antonio Valerio, Annamaria Naggi, Elena Urso and Giangiacomo Torri

Molecules 2012, 17(8), 9912-9930; https://doi.org/10.3390/molecules17089912 - 17 Aug 2012

Cited by 8 | Viewed by 6515

Abstract

This manuscript describes the preparation and the spectroscopic characterisation of semi-synthetic sulfated maltotriose C-C linked dimers (SMTCs) where the natural C-O-C anomeric bond was substituted by one direct central C-C bond. This C-C bond induces conformation and flexibility changes with respect to the [...] Read more.

This manuscript describes the preparation and the spectroscopic characterisation of semi-synthetic sulfated maltotriose C-C linked dimers (SMTCs) where the natural C-O-C anomeric bond was substituted by one direct central C-C bond. This C-C bond induces conformation and flexibility changes with respect to the usual anomeric bond. SMTCs neutral precursors came from maltotriosyl bromide electroreduction through maltotriosyl radical intermediate dimerisation. The new C-C bond configuration, named for convenience a,a, a,b and b,b as the natural anomeric bond, dictated the statistic ratio formation of three diastereoisomers. They were separated by silica gel flash chromatography followed by semi preparative HPLC chromatography. Each diastereoisomer was exhaustively sulfated to afford the corresponding SMTCs. SMTCs were huge characterised by NMR spectroscopy which provided the sulfation degree, too. a,a and a,b were found quite homogeneous samples with a high degree of sulfation (85–95%). b,b appeared a non-homogeneous sample whose average sulfation degree was evaluated at around 78%. Mass spectroscopy experiments confirmed the sulfation degree range. Some considerations were proposed about SMTCs structure-biological properties. Full article

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297 KiB

Open AccessArticle

Synthesis of Disaccharides Containing 6-Deoxy-a-L-talose as Potential Heparan Sulfate Mimetics

by Jon K. Fairweather, Ligong Liu, Tomislav Karoli and Vito Ferro

Molecules 2012, 17(8), 9790-9802; https://doi.org/10.3390/molecules17089790 - 15 Aug 2012

Cited by 10 | Viewed by 8568

Abstract

A 6-deoxy-a-L-talopyranoside acceptor was readily prepared from methyl a-L-rhamnopyranoside and glycosylated with thiogalactoside donors using NIS/TfOH as the promoter to give good yields of the desired a-linked disaccharide (69–90%). Glycosylation with a 2-azido-2-deoxy-D-glucosyl trichloroacetimidate donor was not completely stereoselective (a:b = 6:1), but [...] Read more.

A 6-deoxy-a-L-talopyranoside acceptor was readily prepared from methyl a-L-rhamnopyranoside and glycosylated with thiogalactoside donors using NIS/TfOH as the promoter to give good yields of the desired a-linked disaccharide (69–90%). Glycosylation with a 2-azido-2-deoxy-D-glucosyl trichloroacetimidate donor was not completely stereoselective (a:b = 6:1), but the desired a-linked disaccharide could be isolated in good overall yield (60%) following conversion into its corresponding tribenzoate derivative. The disaccharides were designed to mimic the heparan sulfate (HS) disaccharide GlcN(2S,6S)-IdoA(2S). However, the intermediates readily derived from these disaccharides were not stable to the sulfonation/deacylation conditions required for their conversion into the target HS mimetics. Full article

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444 KiB

Open AccessArticle

Design and Synthesis of a Novel Ganglioside Ligand for Influenza A Viruses ^†

by Tomohiro Nohara, Akihiro Imamura, Maho Yamaguchi, Kazuya I. P. J. Hidari, Takashi Suzuki, Tatsuya Komori, Hiromune Ando, Hideharu Ishida and Makoto Kiso

Molecules 2012, 17(8), 9590-9620; https://doi.org/10.3390/molecules17089590 - 10 Aug 2012

Cited by 10 | Viewed by 7629

Abstract

A novel ganglioside bearing Neua2-3Gal and Neua2-6Gal structures as distal sequences was designed as a ligand for influenza A viruses. The efficient synthesis of the designed ganglioside was accomplished by employing the cassette coupling approach as a key reaction, which was executed between [...] Read more.

A novel ganglioside bearing Neua2-3Gal and Neua2-6Gal structures as distal sequences was designed as a ligand for influenza A viruses. The efficient synthesis of the designed ganglioside was accomplished by employing the cassette coupling approach as a key reaction, which was executed between the non-reducing end of the oligosaccharide and the cyclic glucosylceramide moiety. Examination of its binding activity to influenza A viruses revealed that the new ligand is recognized by Neua2-3 and 2-6 type viruses. Full article

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457 KiB

Open AccessArticle

Accumulation of Unusual Gangliosides G_Q3 and G_P3 in Breast Cancer Cells Expressing the G_D3 Synthase

by Agata Steenackers, Jorick Vanbeselaere, Aurélie Cazet, Marie Bobowski, Yoann Rombouts, Florent Colomb, Xuefen Le Bourhis, Yann Guérardel and Philippe Delannoy

Molecules 2012, 17(8), 9559-9572; https://doi.org/10.3390/molecules17089559 - 10 Aug 2012

Cited by 23 | Viewed by 9314

Abstract

Glycosphingolipids from the ganglio-series are usually classified in four series according to the presence of 0 to 3 sialic acid residues linked to lactosylceramide. The transfer of sialic acid is catalyzed in the Golgi apparatus by specific sialyltransferases that show high specificity toward [...] Read more.

Glycosphingolipids from the ganglio-series are usually classified in four series according to the presence of 0 to 3 sialic acid residues linked to lactosylceramide. The transfer of sialic acid is catalyzed in the Golgi apparatus by specific sialyltransferases that show high specificity toward glycolipid substrates. ST8Sia I (EC 2.4.99.8, SAT-II, SIAT 8a) is the key enzyme controlling the biosynthesis of b- and c-series gangliosides. ST8Sia I is expressed at early developmental stages whereas in adult human tissues, ST8Sia I transcripts are essentially detected in brain. ST8Sia I together with b- and c-series gangliosides are also over-expressed in neuroectoderm-derived malignant tumors such as melanoma, glioblastoma, neuroblastoma and in estrogen receptor (ER) negative breast cancer, where they play a role in cell proliferation, migration, adhesion and angiogenesis. We have stably expressed ST8Sia I in MCF-7 breast cancer cells and analyzed the glycosphingolipid composition of wild type (WT) and GD3S+ clones. As shown by mass spectrometry, MCF-7 expressed a complex pattern of neutral and sialylated glycosphingolipids from globo- and ganglio-series. WT MCF-7 cells exhibited classical monosialylated gangliosides including G_M3, G_M2, and G_M1a. In parallel, the expression of ST8Sia I in MCF-7 GD3S+ clones resulted in a dramatic change in ganglioside composition, with the expression of b- and c-series gangliosides as well as unusual tetra- and pentasialylated lactosylceramide derivatives G_Q3 (II³Neu5Ac₄-Gg₂Cer) and G_P3 (II³Neu5Ac₅-Gg₂Cer). This indicates that ST8Sia I is able to act as an oligosialyltransferase in a cellular context. Full article

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560 KiB

Open AccessArticle

Synthesis, Antigenicity Against Human Sera and Structure-Activity Relationships of Carbohydrate Moieties from Toxocara larvae and Their Analogues

by Akihiko Koizumi, Kimiaki Yamano, Takashi Tsuchiya, Frank Schweizer, Fumiyuki Kiuchi and Noriyasu Hada

Molecules 2012, 17(8), 9023-9042; https://doi.org/10.3390/molecules17089023 - 30 Jul 2012

Cited by 11 | Viewed by 6702

Abstract

Stereocontrolled syntheses of biotin-labeled oligosaccharide portions containing the Galβ1-3GalNAc core of the TES-glycoprotein antigen obtained from larvae of the parasite Toxocara and their analogues have been accomplished. Trisaccharides Fuc2Meα1-2Gal4Meβ1-3GalNAcα1-OR (A), Fucα1-2Gal4Meβ1-3GalNAcα1-OR (B), Fuc2Meα1-2Galβ1-3GalNAcα1-OR (C), Fucα1-2Galβ1-3GalNAcα1-OR (D [...] Read more.

Stereocontrolled syntheses of biotin-labeled oligosaccharide portions containing the Galβ1-3GalNAc core of the TES-glycoprotein antigen obtained from larvae of the parasite Toxocara and their analogues have been accomplished. Trisaccharides Fuc2Meα1-2Gal4Meβ1-3GalNAcα1-OR (A), Fucα1-2Gal4Meβ1-3GalNAcα1-OR (B), Fuc2Meα1-2Galβ1-3GalNAcα1-OR (C), Fucα1-2Galβ1-3GalNAcα1-OR (D) and a disaccharide Fuc2Meα1-2Gal4Meβ1-OR (E) (R = biotinylated probe) were synthesized by block synthesis using 5-(methoxycarbonyl)pentyl-2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1®3)-2-azide-4-O-benzyl-2-deoxy-α-D-galactopyranoside as a common glycosyl acceptor. We examined the antigenicity of these five oligosaccharides by enzyme linked immunosorbent assay (ELISA). Our results demonstrate that the O-methyl groups in these oligosaccharides are important for their antigenicity and the biotinylated oligosaccharides A, B, C and E have high serodiagnostic potential to detect infections caused by Toxocara larvae. Full article

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230 KiB

Open AccessArticle

Synthesis and Sensory Evaluation of ent-Kaurane Diterpene Glycosides

by Indra Prakash, Mary Campbell, Rafael Ignacio San Miguel and Venkata Sai Prakash Chaturvedula

Molecules 2012, 17(8), 8908-8916; https://doi.org/10.3390/molecules17088908 - 26 Jul 2012

Cited by 18 | Viewed by 8854

Abstract

Catalytic hydrogenation of the three ent-kaurane diterpene glycosides isolated from Stevia rebaudiana, namely rubusoside, stevioside, and rebaudioside-A has been carried out using Pd(OH)₂ and their corresponding dihydro derivatives have been isolated as the products. Synthesis of reduced steviol glycosides was [...] Read more.

Catalytic hydrogenation of the three ent-kaurane diterpene glycosides isolated from Stevia rebaudiana, namely rubusoside, stevioside, and rebaudioside-A has been carried out using Pd(OH)₂ and their corresponding dihydro derivatives have been isolated as the products. Synthesis of reduced steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR spectral data and chemical studies. Also, we report herewith the sensory evaluation of all the reduced compounds against their corresponding original steviol glycosides and sucrose for the sweetness property of these molecules. Full article

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696 KiB

Open AccessArticle

Application of Paramagnetic NMR-Validated Molecular Dynamics Simulation to the Analysis of a Conformational Ensemble of a Branched Oligosaccharide

by Ying Zhang, Sayoko Yamamoto, Takumi Yamaguchi and Koichi Kato

Molecules 2012, 17(6), 6658-6671; https://doi.org/10.3390/molecules17066658 - 31 May 2012

Cited by 37 | Viewed by 7378

Abstract

Oligosaccharides of biological importance often exhibit branched covalent structures and dynamic conformational multiplicities. Here we report the application of a method that we developed, which combined molecular dynamics (MD) simulations and lanthanide-assisted paramagnetic NMR spectroscopy, to evaluate the dynamic conformational ensemble of a [...] Read more.

Oligosaccharides of biological importance often exhibit branched covalent structures and dynamic conformational multiplicities. Here we report the application of a method that we developed, which combined molecular dynamics (MD) simulations and lanthanide-assisted paramagnetic NMR spectroscopy, to evaluate the dynamic conformational ensemble of a branched oligosaccharide. A lanthanide-chelating tag was attached to the reducing end of the branched tetrasaccharide of GM2 ganglioside to observe pseudocontact shifts as the source of long distance information for validating the conformational ensemble derived from MD simulations. By inspecting the results, the conformational space of the GM2 tetrasaccharide was compared with that of its nonbranched derivative, the GM3 trisaccharide. Full article

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219 KiB

Open AccessArticle

Glycosylation of Vanillin and 8-Nordihydrocapsaicin by Cultured Eucalyptus perriniana Cells

by Daisuke Sato, Yuki Eshita, Hisashi Katsuragi, Hiroki Hamada, Kei Shimoda and Naoji Kubota

Molecules 2012, 17(5), 5013-5020; https://doi.org/10.3390/molecules17055013 - 2 May 2012

Cited by 9 | Viewed by 7093

Abstract

Glycosylation of vanilloids such as vanillin and 8-nordihydrocapsaicin by cultured plant cells of Eucalyptus perriniana was studied. Vanillin was converted into vanillin 4-O-b-D-glucopyranoside, vanillyl alcohol, and 4-O-b-D-glucopyranosylvanillyl alcohol by E. perriniana cells. Incubation of cultured E. perriniana cells with [...] Read more.

Glycosylation of vanilloids such as vanillin and 8-nordihydrocapsaicin by cultured plant cells of Eucalyptus perriniana was studied. Vanillin was converted into vanillin 4-O-b-D-glucopyranoside, vanillyl alcohol, and 4-O-b-D-glucopyranosylvanillyl alcohol by E. perriniana cells. Incubation of cultured E. perriniana cells with 8-nor- dihydrocapsaicin gave 8-nordihydrocapsaicin 4-O-b-D-glucopyranoside and 8-nordihydro- capsaicin 4-O-b-D-gentiobioside. Full article

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310 KiB

Open AccessArticle

1D ¹³C-NMR Data as Molecular Descriptors in Spectra — Structure Relationship Analysis of Oligosaccharides

by Florbela Pereira

Molecules 2012, 17(4), 3818-3833; https://doi.org/10.3390/molecules17043818 - 28 Mar 2012

Cited by 3 | Viewed by 7737

Abstract

Spectra-structure relationships were investigated for estimating the anomeric configuration, residues and type of linkages of linear and branched trisaccharides using ¹³C-NMR chemical shifts. For this study, 119 pyranosyl trisaccharides were used that are trimers of the α or β anomers of D-glucose, [...] Read more.

Spectra-structure relationships were investigated for estimating the anomeric configuration, residues and type of linkages of linear and branched trisaccharides using ¹³C-NMR chemical shifts. For this study, 119 pyranosyl trisaccharides were used that are trimers of the α or β anomers of D-glucose, D-galactose, D-mannose, L-fucose or L-rhamnose residues bonded through a or b glycosidic linkages of types 1→2, 1→3, 1→4, or 1→6, as well as methoxylated and/or N-acetylated amino trisaccharides. Machine learning experiments were performed for: (1) classification of the anomeric configuration of the first unit, second unit and reducing end; (2) classification of the type of first and second linkages; (3) classification of the three residues: reducing end, middle and first residue; and (4) classification of the chain type. Our previously model for predicting the structure of disaccharides was incorporated in this new model with an improvement of the predictive power. The best results were achieved using Random Forests with 204 di- and trisaccharides for the training set—it could correctly classify 83%, 90%, 88%, 85%, 85%, 75%, 79%, 68% and 94% of the test set (69 compounds) for the nine tasks, respectively, on the basis of unassigned chemical shifts. Full article

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