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Göteborgs universitets publikationer

Studies on gangliosides with affinity for Helicobacter pylori: binding to natural and chemically modified structures.

Författare och institution:
Halina Miller-Podraza (Institutionen för medicinsk och fysiologisk kemi); Petra Johansson (Institutionen för medicinsk och fysiologisk kemi); Jonas Ångström (Institutionen för medicinsk och fysiologisk kemi); Thomas Larsson (Institutionen för medicinsk och fysiologisk kemi); Marianne Longard (Institutionen för medicinsk och fysiologisk kemi); Karl-Anders Karlsson (Institutionen för medicinsk och fysiologisk kemi)
Publicerad i:
Glycobiology, 14 ( 3 ) s. 205-17
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Helicobacter pylori, like many other microbes, has the ability to bind to carbohydrate epitopes. Several sugar sequences have been reported as active for the bacterium, including some neutral, sulfated, and sialylated structures. We investigated structural requirements for the sialic acid-dependent binding using a number of natural and chemically modified gangliosides. We have chosen for derivatization studies two kinds of binding-active glycolipids, the simple ganglioside S-3PG (Neu5Ac alpha 3Gal beta 4GlcNAc beta 3Gal beta 4Glc beta 1Cer, sialylparagloboside) and branched polyglycosylceramides (PGCs) of human origin. The modifications included oxidation of the sialic acid glycerol chain, reduction of the carboxyl group, amidation of the carboxyl group, and lactonization. Binding experiments confirmed a preference of H. pylori for 3-linked sialic acid and penultimate 4-linked galactose. As expected, neolacto gangliosides (with Gal beta 4GlcNAc in the core structure) were active in our assays, whereas gangliosides with lacto (Gal beta 3GlcNAc) and ganglio (Gal beta 3GalNAc) carbohydrate chains were not. Negative binding results were also obtained for disialylparagloboside (with terminal NeuAc alpha 8NeuAc) and NeuAc alpha 6-containing glycolipids. Chemical studies revealed dependence of the binding on Neu5Ac and its glycerol and carboxyl side chains. Most of the derivatizations performed on these groups abolished the binding; however, some of the amide forms turned out to be active, and one of them (octadecylamide) was found to be an excellent binder. The combined data from molecular dynamics simulations indicate that the binding-active configuration of the terminal disaccharide of S-3PG is with the sialic acid in the anticlinal conformation, whereas in branched PGCs the same structural element most likely assumes the synclinal presentation.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Binding Sites, Carbohydrate Conformation, Chromatography, Thin Layer, Gangliosides, chemical synthesis, chemistry, metabolism, Helicobacter pylori, metabolism, Humans, Models, Molecular, Spectrometry, Mass, Electrospray Ionization, Spectrometry, Mass, Fast Atom Bombardment
Postens nummer:
Posten skapad:
2007-11-07 13:32

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