| 1. |
- Dahlqvist, Alexander, et al.
(författare)
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Stereo- And regioselective hydroboration of 1-exo-methylene pyranoses : Discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors
- 2019
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Ingår i: Beilstein Journal of Organic Chemistry. - : Beilstein Institut. - 1860-5397. ; 15, s. 1046-1060
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Tidskriftsartikel (refereegranskat)abstract
- Galectins are carbohydrate recognition proteins that bind carbohydrates containing galactose and are involved in cell signaling and cellular interactions, involving them in several diseases. We present the synthesis of (aryltriazolyl)methyl galactopyranoside galectin inhibitors using a highly diastereoselective hydroboration of C1-exo-methylene pyranosides giving inhibitors with fourfold or better selectivity for galectin-1 over galectin-3, -4C (C-terminal CRD), -4N (N-terminal CRD), -7, -8C, -8N, -9C, and -9N and dissociation constants down to 170 μM.
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| 2. |
- Furevi, Axel, 1992-, et al.
(författare)
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Complete 1H and 13C NMR chemical shift assignments of mono-to tetrasaccharides as basis for NMR chemical shift predictions of oligo- and polysaccharides using the computer program CASPER
- 2022
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Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 513
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Tidskriftsartikel (refereegranskat)abstract
- Carbohydrate structure can be elucidated or confirmed by using NMR spectroscopy as the prime technique. Prediction of 1H and 13C NMR chemical shifts by computational approaches makes this assignment process more efficient and the program CASPER can perform this task rapidly. It does so by relying on chemical shift data of mono-, di-, and trisaccharides. In order to improve accuracy and quality of these predictions we have assigned 1H and 13C NMR chemical shifts of 30 monosaccharides, 17 disaccharides, 10 trisaccharides and one tetrasaccharide; in total 58 compounds. Due to different rotamers, ring forms, α- and β-anomeric forms and pD conditions this resulted in 74 1H and 13C NMR chemical shift data sets, all of which were refined using total line-shape analysis for the 1H resonances in order to obtain accurate chemical shifts. Subsequent NMR chemical shift predictions for three sialic acid-containing oligosaccharides, viz., GD1a, a disialyl-LNnT hexasaccharide and a polysialic acid-lactose decasaccharide, and NMR-based structural elucidations of two O-antigen polysaccharides from E. coli O174 were performed by the CASPER program (http://www.casper.organ.su.se/casper/) resulting in very good to excellent agreement between experimental and predicted data thereby demonstrating its utility for carbohydrate compounds that have been chemically or enzymatically synthesized, structurally modified or isolated from nature.
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| 3. |
- Furevi, Axel, 1992-, et al.
(författare)
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Elucidation of the O-antigen structure of Escherichia coli O93 and characterization of its biosynthetic genes
- 2023
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 33:4, s. 289-300
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the O-antigen from the international reference strain Escherichia coli O93:-:H16 has been determined. A nonrandom modal chain-length distribution was observed for the lipopolysaccharide, a pattern which is typical when long O-specific polysaccharides are expressed. By a combination of (i) bioinformatics information on the gene cluster related to O-antigen synthesis including putative function on glycosyl transferases, (ii) the magnitude of NMR coupling constants of anomeric protons, and (iii) unassigned 2D H-1, C-13-HSQC, and H-1,H-1-TOCSY NMR spectra it was possible to efficiently elucidate the structure of the carbohydrate polymer in an automated fashion using the computer program CASPER. The polysaccharide also carries O-acetyl groups and their locations were determined by 2D NMR experiments showing that similar to 1/2 of the population was 2,6-di-O-acetylated, similar to 1/4 was 2-O-acetylated, whereas similar to 1/4 did not carry O-acetyl group(s) in the 3-O-substituted mannosyl residue of the repeating unit. The structure of the tetrasaccharide repeating unit of the O-antigen is given by: -> 2)-beta-D-Manp-(1 -> 3)-beta-D-Manp2Ac6Ac-(1 -> 4)-beta-D-GlcpA-(1 -> 3)-alpha-D-GlcpNAc-(1 ->, which should also be the biological repeating unit and it shares structural elements with capsular polysaccharides from E. coli K84 and K50. The structure of the acidic O-specific polysaccharide from Cellulophaga baltica strain NN015840(T) differs to that of the O-antigen from E. coli O93 by lacking the O-acetyl group at O6 of the O-acetylated mannosyl residue.
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| 4. |
- Furevi, Axel, et al.
(författare)
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Structural analysis of the O-antigen polysaccharide from Escherichia coli O188
- 2020
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Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 498
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the O-antigen from Escherichia coli reference strain O188 (E. coli O188:H10) has been investigated. The lipopolysaccharide shows a typical nonrandom modal chain-length distribution and the sugar and absolute configuration analysis revealed D-Man, D-Glc, D-GlcN and D-GlcA as major components. The structure of the O-specific polysaccharide was determined using one- and two-dimensional H-1 and C-13 NMR spectroscopy experiments, where inter-residue correlations were identified by H-1,C-13-heteronuclear multiple-bond correlation and H-1,H-1-NOESY experiments, which revealed that it consists of pentasaccharide repeating units with the -> 4)-beta-D-GlcpA-(1 -> 2)-beta-D-Manp-(1 -> 4)-beta-D-Manp-(1 -> 3)-beta-D-GlcpNAc-(1 -> following structure: vertical bar alpha-D-Galp-(1 -> 3) Biosynthetic aspects and NMR analysis are consistent with the presented structure as the biological repeating unit. The O-antigen of Shigella boydii type 16 differs only in that it carries O-acetyl groups to similar to 50% at O6 of the branchpoint mannose residues. A molecular model of the E. coli O188 O-antigen containing 20 repeating units extends similar to 100 angstrom, which is similar to the height of the periplasmic portion of polysaccharide co-polymerase Wzz proteins that regulate the O-antigen chain length of lipopolysaccharides in the Wzx/Wzy biosynthetic pathway.
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| 5. |
- Furevi, Axel, 1992-
(författare)
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Structural and Conformational Analysis of Bacterial Polysaccharides using NMR Spectroscopy
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Carbohydrates is one of the three classes of biomolecules found in nature. It is the most common one in comparison to the other two classes, lipids and proteins. However, this simple categorization does not reflect the reality since carbohydrates often are covalently linked to e.g., proteins, so-called glycoproteins where, for example, N-glycans are used as markers of quality control during the process of protein folding. Another example is lipopolysaccharides, which cover the cell surfaces of gram-negative bacteria and which contain both a lipid moiety (Lipid A) and a carbohydrate chain. The outer part of the carbohydrate chain is a polysaccharide, also called O-antigen, as it interacts with the immune system of the host. The polysaccharide has, like a polymer, a repeating unit consisting of 2-7 monosaccharides. The repeating unit varies between different bacteria. Determining the structure of these polysaccharides is important in order to be able to categorize the various strains that exist, but also to be able to develop future glycoconjugate vaccines. This is important as the WHO estimates that antibiotic resistance is expected to be more lethal than cancer by 2050, and therefore a vaccine is needed to slow down this development.Nuclear Magnetic Resonance Spectroscopy (NMR) is a useful analytical tool to analyze these carbohydrates at the atomic level in order to determine their structures.The first part (Paper I-III) of this thesis will summarize the structural determination of three Escherichia coli serogroups with hitherto unknown lipopolysaccharides.The second part (Paper IV) will discuss the structure determination, using NMR spectroscopy, for various mono-, di-, and tri-saccharides that have recently been implemented in the structure-determination program, CASPER. The chapter will also present examples of predictions of complex carbohydrates that CASPER can perform.The third part (Paper V) of the thesis will investigate conformational aspects of the polysaccharides from Shigella flexneri serotypes 7a and 7b using NMR spectroscopy and molecular dynamics simulations.
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| 6. |
- Furevi, Axel, 1992-, et al.
(författare)
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Structural elucidation of the O-antigen polysaccharide from Escherichia coli O125ac and biosynthetic aspects thereof
- 2022
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 32:12, s. 1089-1100
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Tidskriftsartikel (refereegranskat)abstract
- Enteropathogenic Escherichia coli O125, the cause of infectious diarrheal disease, is comprised of two serogroups, viz., O125ab and O125ac, which display the aggregative adherence pattern with epithelial cells. Herein, the structure of the O-antigen polysaccharide from E. coli O125ac:H6 has been elucidated. Sugar analysis revealed the presence of fucose, mannose, galactose and N-acetyl-galactosamine as major components. Unassigned 1H and 13C NMR data from one- and two-dimensional NMR experiments of the O125ac O-antigen in conjunction with sugar components were used as input to the CASPER program, which can determine polysaccharide structure in a fully automated way, and resulted in the following branched pentasaccharide structure of the repeating unit: →4)[β-D-Galp-(1 → 3)]-β-D-GalpNAc-(1 → 2)-α-D-Manp-(1 → 3)-α-L-Fucp-(1 → 3)-α-D-GalpNAc-(1→, where the side chain is denoted by square brackets. The proposed O-antigen structure was confirmed by 1H and 13C NMR chemical shift assignments and determination of interresidue connectivities. Based on this structure, that of the O125ab O-antigen, which consists of hexasaccharide repeating units with an additional glucosyl group, was possible to establish in a semi-automated fashion by CASPER. The putative existence of gnu and gne in the gene clusters of the O125 serogroups is manifested by N-acetyl-D-galactosamine residues as the initial sugar residue of the biological repeating unit as well as within the repeating unit. The close similarity between O-antigen structures is consistent with the presence of two subgroups in the E. coli O125 serogroup.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Liu, Bin, et al.
(författare)
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Structure and genetics of Escherichia coli O antigens
- 2020
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Ingår i: FEMS Microbiology Reviews. - : Oxford University Press (OUP). - 0168-6445 .- 1574-6976. ; 44:6, s. 655-683
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Forskningsöversikt (refereegranskat)abstract
- Escherichia coli includes clonal groups of both commensal and pathogenic strains, with some of the latter causing serious infectious diseases. O antigen variation is current standard in defining strains for taxonomy and epidemiology, providing the basis for many serotyping schemes for Gram-negative bacteria. This review covers the diversity in E. coli O antigen structures and gene clusters, and the genetic basis for the structural diversity. Of the 187 formally defined O antigens, six (O31, O47, O67, O72, O94 and O122) have since been removed and three (O34, O89 and O144) strains do not produce any O antigen. Therefore, structures are presented for 176 of the 181 E. coli O antigens, some of which include subgroups. Most (93%) of these O antigens are synthesized via the Wzx/Wzy pathway, 11 via the ABC transporter pathway, with O20, O57 and O60 still uncharacterized due to failure to find their O antigen gene clusters. Biosynthetic pathways are given for 38 of the 49 sugars found in E. coli O antigens, and several pairs or groups of the E. coli antigens that have related structures show close relationships of the O antigen gene clusters within clades, thereby highlighting the genetic basis of the evolution of diversity.
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