| 1. |
- Buts, L, et al.
(author)
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Solving the phase problem for carbohydrate-binding proteins using selenium derivatives of their ligands : a case study involving the bacterial F17-G adhesin
- 2003
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In: Acta Crystallographica Section D. - : International Union of Crystallography (IUCr). - 2059-7983. ; 59:6, s. 1012-1015
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Journal article (peer-reviewed)abstract
- The Escherichia coli adhesin F17-G is a carbohydrate-binding protein that allows the bacterium to attach to the intestinal epithelium of young ruminants. The structure of the 17 kDa lectin domain of F17-G was determined using the anomalous dispersion signal of a selenium-containing analogue of the monosaccharide ligand N-acetyl-D-glucosamine in which the anomeric oxygen was replaced by an Se atom. A three-wavelength MAD data set yielded good experimental phases to 2.6 Angstrom resolution. The structure was refined to 1.75 Angstrom resolution and was used to solve the structures of the ligand-free protein and the F17-G-N-acetyl-D-glucosamine complex. This selenium-carbohydrate phasing method could be of general use for determining the structures of carbohydrate-binding proteins.
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| 2. |
- Buts, L, et al.
(author)
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The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine
- 2003
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In: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 49:3, s. 705-715
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Journal article (peer-reviewed)abstract
- The F17-G adhesin at the tip of flexible F17 fimbriae of enterotoxigenic Escherichia coli mediates binding to N-acetyl-beta-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants. We report the 1.7 Angstrom resolution crystal structure of the lectin domain of F17-G, both free and in complex with N-acetylglucosamine. The monosaccharide is bound on the side of the ellipsoid-shaped protein in a conserved site around which all natural variations of F17-G are clustered. A model is proposed for the interaction between F17-fimbriated E. coli and microvilli with enhanced affinity compared with the binding constant we determined for F17-G binding to N-acetylglucosamine (0.85 mM(-1)). Unexpectedly, the F17-G structure reveals that the lectin domains of the F17-G, PapGII and FimH fimbrial adhesins all share the immunoglobulin-like fold of the structural components (pilins) of their fimbriae, despite lack of any sequence identity. Fold comparisons with pilin and chaperone structures of the chaperone/usher pathway highlight the central role of the C-terminal beta-strand G of the immunoglobulin-like fold and provides new insights into pilus assembly, function and adhesion.
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| 3. |
- Chakroborty, Anand, et al.
(author)
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Modified Hederagenin Derivatives Demonstrate Ex Vivo Anthelmintic Activity against Fasciola hepatica
- 2023
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In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 15:7
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Journal article (peer-reviewed)abstract
- Infection with Fasciola hepatica (liver fluke) causes fasciolosis (or fascioliasis) and poses a considerable economic as well as welfare burden to both the agricultural and animal health sectors. Here, we explore the ex vivo anthelmintic potential of synthetic derivatives of hederagenin, isolated in bulk from Hedera helix. Thirty-six compounds were initially screened against F. hepatica newly excysted juveniles (NEJs) of the Italian strain. Eleven of these compounds were active against NEJs and were selected for further study, using adult F. hepatica derived from a local abattoir (provenance unknown). From these eleven compounds, six demonstrated activity and were further assessed against immature liver flukes of the Italian strain. Subsequently, the most active compounds (n = 5) were further evaluated in ex vivo dose response experiments against adult Italian strain liver flukes. Overall, MC042 was identified as the most active molecule and the EC50 obtained from immature and adult liver fluke assays (at 24 h post co-culture) are estimated as 1.07 & mu;M and 13.02 & mu;M, respectively. When compared to the in vitro cytotoxicity of MDBK bovine cell line, MC042 demonstrated the highest anthelmintic selectivity (44.37 for immature and 3.64 for adult flukes). These data indicate that modified hederagenins display properties suitable for further investigations as candidate flukicides.
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| 4. |
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| 5. |
- Lahmann, Martina, Docent i kemi, 1963-, et al.
(author)
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A facile approach to diosgenin and furostan type saponins bearing a 3 beta-chacotriose moiety
- 2002
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In: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 337:21-23, s. 2153-2159
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Journal article (peer-reviewed)abstract
- Combination of a one-pot coupling technique and the use of benzyl ethers as permanent protecting groups offered a short and simple route to dioscin-type saponins. This strategy in combination with a mild reductive opening procedure of the spiroketal function in diosgenin also offered a convenient approach to bidesmosidic furostan type saponins. (Me3NBH3)-B-./AlCl3 promoted acetal opening of 3-O-TBDMS-protected diosgenin gave the 26-OH acceptor 9 into which a benzylated beta-glucose moiety was introduced by a S(N)2-type imidate coupling. After cleavage of the silyl ether, the 3beta-O-glucose and the 4-O-linked rhamnose of the chacotriose unit were introduced by a NIS/AgOTf-promoted one-pot coupling sequence utilising thioglycoside donors and their different reactivity in different solvents. After removal of a benzoyl group, the same coupling conditions were also used for the coupling of the second 2-O-linked rhamnose unit. The target substance was obtained after cleavage of the protecting benzyl ethers under Birch-type conditions, which did not affect the double bond in the steroid skeleton.
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| 6. |
- Lahmann, Martina, Docent i kemi, 1963-, et al.
(author)
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Investigation of the reactivity difference between thioglycoside donors with variant aglycon parts
- 2002
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In: Canadian journal of chemistry (Print). - Univ Stockholm, Arrhenius Lab, Dept Organ Chem, S-10691 Stockholm, Sweden. : Canadian Science Publishing. - 0008-4042 .- 1480-3291. ; 80:8, s. 889-893
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Journal article (peer-reviewed)abstract
- The reactivity of perbenzoylated thioglycosides with various thiol aglycons has been compared and quantified using competitive glycosylation experiments. Methyl 2,3,4-tri-O-benzyl-alpha-D-glucopyranoside was employed as acceptor and DMTST as a promoter. The reactivity was found, as expected, to depend on the electron donating properties of the aglycon. Hence, the most reactive donor, the cyclohexyl thioglycoside, was found to be about three times as reactive as the thioethyl glycoside, which in turn was twice as reactive as the thiomethyl donor. The thiophenyl donor was even less reactive, whereas p-halophenyl donors were inert under the glycosylation conditions used - but could be activated using NIS-TfOH as promoter. Furthermore, it was found that galactosyl donors were three to four times more reactive than the corresponding glucosyl derivative. These results allowed the design of an orthogonal coupling between thioglycosides with the same protecting groups (benzoyls) but with different thiol aglycons.
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| 7. |
- Lahmann, Martina, Docent i kemi, 1963-, et al.
(author)
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One-pot oligosaccharide synthesis exploiting solvent reactivity effects
- 2000
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In: Organic Letters. - Univ Stockholm, Arrhenius Lab, Dept Organ Chem, S-10691 Stockholm, Sweden. : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 2:24, s. 3881-3882
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Journal article (peer-reviewed)abstract
- One-pot syntheses of trisaccharides have been accomplished simply by changing the solvent system between the two subsequent glycosylation reactions and utilizing the difference in glycosylation rate between different solvents. By tuning the reactivity of accepters and donors and performing the first glycosylation in Et2O (low glycosylation rate) and the second in CH2Cl2/Et2O (higher glycosylation rate), trisaccharides were synthesized in high yields (76-84%).
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| 8. |
- Lahmann, Martina, Docent i kemi, 1963-, et al.
(author)
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Synthesis of a polyphosphorylated GPI-anchor core structure
- 2002
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In: Canadian journal of chemistry (Print). - : Canadian Science Publishing. - 0008-4042 .- 1480-3291. ; 80:8, s. 1105-1111
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Journal article (peer-reviewed)abstract
- Using a linear assembly approach a highly differentially protected derivative of the common GPI-anchor core structure (alpha-D-Man-(1-->6)-alpha-D-Man-(1-->2)-alpha-D-Man-(1-->4)-alpha-D-GlcNH(2)-(1-->6)-D-myo-inositol) has been synthesized. All mannose donors were prepared from a common thioglycoside precursor (1), and coupled to GlcN(3)-myo-inositol acceptor 5 in a linear five-step glycosylation-deprotection sequence in 49% overall yield, to give the key intermediate 10, with orthogonal temporary protecting groups at the 6", 2", 6', and 2 positions of the trimannoside motif and at the 1 and 2 positions of the inositol part. Consecutive removal of the temporary protecting groups in the trimannoside moiety followed by phosphorylation, gave a tetraphosphosphate derivative in 60% overall yield. Removal of a camphor acetal afforded a 1,2-inositol diol, which was converted to a 1,2-cyclic phosphate using commercial methyl dichlorophosphate (-->17, 95%). One-step deprotection using sodium in liquid ammonia afforded the target polyphosphorylated core structure 18 (60%), which will be tested for metabolic insulin action.
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| 9. |
- Lahmann, Martina, Docent i kemi, 1963-, et al.
(author)
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Synthesis of alpha-tocopheryl oligosaccharides
- 1997
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In: Carbohydrate Research. - UNIV HAMBURG,INST ORGAN CHEM,D-20146 HAMBURG,GERMANY. : Elsevier BV. - 0008-6215 .- 1873-426X. ; 299:1-2, s. 23-31
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Journal article (peer-reviewed)abstract
- As effective natural antioxidants, tocopherols and also their esters are frequently added to foodstuffs, pharmaceuticals and cosmetics. For increase of polarity, hence solubility in water, a series of alpha-tocopheryl oligosaccharides was synthesised using BF3-etherate. The pure alpha-tocopheryl beta-maltotetraoside as well as the higher homologues proved to be water-soluble.
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| 10. |
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