| 1. |
- Bugaytsova, Jeanna, et al.
(författare)
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pH regulated H. pylori adherence : implications for persistent infection and disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Helicobacter pylori’s BabA adhesin binds strongly to gastric mucosal ABH/Leb glycans on the stomach epithelium and overlying mucus, materials continuously shed into the acidic gastric lumen. Here we report that this binding is acid labile, acid inactivation is fully reversible; and acid lability profiles vary with BabA sequence and correlate with disease patterns. Isogenic H. pylori strains from the gastric antrum and more acidic corpus were identified that differed in acid lability of receptor binding and in sequence near BabA’s carbohydrate binding domain. We propose that reversible acid inactivation of receptor binding helps H. pylori avoid clearance by mucosal shedding, and that strain differences in acid lability affect tissue tropism and the spectrum of associated gastric diseases.
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| 2. |
- Svedhem, Sofia, et al.
(författare)
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Synthesis and self-assembly of globotriose derivatives : A model system for studies of carbohydrate-protein interactions
- 2002
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 18:7, s. 2848-2858
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Tidskriftsartikel (refereegranskat)abstract
- Self-assembled monolayers (SAMs) on gold exposing a-D-Galp-(1 ? 4)-ß-D-Galp-(1?4)-ß-D-Glcp (globotriose) are described. A synthetic pathway for the preparation of the bioactive carbohydrate globotriose coupled directly to bis(16-hydroxyhexadecanyl) disulfide ((HOC16H32S)2), as well as via tetra- or di(ethylene glycol) spacers, was developed. The SAMs were characterized by ellipsometry, contact angle goniometry, infrared reflection-absorption spectroscopy, and by their interactions with monoclonal antibodies. The ellipsometry measurements of mixed SAMs revealed thicknesses between 22 and 40 Å, depending on the ratio between carbohydrate and non-carbohydrate disulfides in the preparation solution. When the solution contained 10% or more of the carbohydrate adsorbate, the modified gold substrates displayed total wetting. Infrared reflection-absorption spectroscopy conferred well-ordered SAMs with a high degree of crystallinity. Furthermore, two monoclonal antibodies (IgM, MAHI 419 and IgG, MAHI 5) showed different affinity for mixed SAMs depending on the fraction and the structure of the carbohydrate component used (globotriose or globotriose tetra(ethylene glycol)), with the largest amount of protein bound for MAHI 419 at 1-10% of surface carbohydrate. These results demonstrate the usefulness of the SAM approach to explore molecular details such as the effect of a spacer or antigen distribution on antibody interactions at interfaces.
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| 3. |
- Adrian Meredith, Jenny, 1971-, et al.
(författare)
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Design and synthesis of novel P2 substituents in diol-based HIV protease inhibitors
- 2010
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 45:1, s. 160-170
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and SAR of HIV-1 protease inhibitors containing novel P2 structural elements are presented. The inhibitors were designed having hydrogen bond accepting P2 substituents to probe potential favorable interactions to Asp-29/Asp-30 of the HIV-1 protease backbone utilizing inhibitor 3 as a model template. Several inhibitors were synthesized from an L-Val methyl amide P2 motif by appending hydrogen bonding moieties from either the isopropyl side-chain or from the methyl amide portion. The most promising inhibitors 4a and 4e displayed K-i values of 1.0 nM and 0.7 nM respectively and EC50 values in the MT4 cell-based assay of 0.17 mu M and 0.33 mu M respectively, a slight loss in potency compared to lead inhibitor 3. These inhibitors were also tested against an HIV protease inhibitor resistant strain carrying the M461, V82F, and 184V mutations. Inhibitors 4a and 4e displayed a 3 and 4 fold change respectively compared with HIV wild type, whereas lead inhibitor 3 showed a higher 9 fold change. This study further demonstrate the chemical tractability of the approach where various P2 substituents can be introduced in just one chemical step from lactone 21 enabling facile modifications of the overall properties in this inhibitor class.
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| 4. |
- Andersson, Claes-Henrik, et al.
(författare)
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Reversible Non-Covalent Derivatisation of Carbon Nanotubes with Glycosides
- 2009
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Ingår i: Soft Matter. - 1744-683X. ; 5:14, s. 2713-2716
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Tidskriftsartikel (refereegranskat)abstract
- SWNTs and MWNTs have been non-covalently functionalized with glycosides in a reversible manner, and fluorescence titrations have been used to quantify the formed supramolecular assemblies which for SWNTs exhibits increased water solubility.
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| 5. |
- Andersson, Claes-Henrik, et al.
(författare)
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Reversible non-covalent derivatisation of carbon nanotubes with glycosides
- 2009
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 5:14, s. 2713-2716
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Tidskriftsartikel (refereegranskat)abstract
- SWNTs and MWNTs have been non-covalently functionalized with glycosides in a reversible manner, and fluorescence titrations have been used to quantify the formed supramolecular assemblies which for SWNTs exhibits increased water solubility.
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| 6. |
- Andre, Sabine, et al.
(författare)
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Glycocluster Design for Improved Avidity and Selectivity in Blocking Human Lectin/Plant Toxin Binding to Glycoproteins and Cells
- 2010
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 7:6, s. 2270-2279
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Tidskriftsartikel (refereegranskat)abstract
- Blocking lectin/toxin binding to human cells by suitable inhibitors can therapeutically protect them from harmful effects. Clustered design of ligand presentation holds the promise of affinity increase relative to the free sugar and inherent selectivity among lectin targets. Using first a solid-phase assay with a glycoprotein presenting N-glycans as lectin-reactive probe, we assessed the inhibitory potency of bi- to tetravalent clusters on a plant toxin and three human adhesion/growth-regulatory lectins. Enhanced avidity relative to the free sugar was detected together with lectin-type selectivity. These effects were confirmed on the level of cells in vitro, also for two leguminous lectins. The lack of toxicity in cell proliferation assays excluded concerns to further work on these compounds. The given cluster design and the strategic combination of the two assay systems of increasing biorelevance will thus be helpful to take the next steps in drug development, e.g. tailoring the sugar headgroup.
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| 7. |
- Arewang, Carl Johan, et al.
(författare)
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Synthesis of urine drug metabolites : glucuronic acid glycosides of phenol intermediates
- 2007
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Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 342:7, s. 970-974
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Tidskriftsartikel (refereegranskat)abstract
- The investigation of drug metabolism requires substantial amount of metabolites. Isolation from urine is tedious, therefore, the material obtained by synthesis is preferred. Substantial amounts of three tentative drug metabolites, phenolic glucuronides, have been prepared using easily available glycosyl donors. The final products [3(2-N-methyl-N-isopropylaminoethoxy)phenyl] beta-D-glucopyranosiduronic acid, 4-amino-3,5-dimethylphenyl beta-D-glucopyranosiduronic acid and [2(S)-propanoyl-6-O-naphthyl] beta-D-glucopyranuronic acid are useful as, for example, reference material in metabolite investigations.
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| 8. |
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| 9. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 10. |
- Bernardi, Anna, et al.
(författare)
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Multivalent glycoconjugates as anti-pathogenic agents
- 2013
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Ingår i: Chemical Society Reviews. - : Royal Society of Chemistry (RSC). - 0306-0012 .- 1460-4744. ; 42:11, s. 4709-4727
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Forskningsöversikt (refereegranskat)abstract
- Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein-glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies.
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