Glycobiology Advance Access originally published online on November 24, 2003
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Glycobiology vol 14 no 3 pp. 205-217, 2004
Glycobiology vol. 14 no. 3 © Oxford University Press 2004; all rights reserved.
Studies on gangliosides with affinity for Helicobacter pylori: binding to natural and chemically modified structures
Institute of Medical Biochemistry, Göteborg University, PO Box 440, SE 405 30 Göteborg, Sweden
Received on June 24, 2003; revised on October 17, 2003; accepted on November 11, 2003
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
3Galß4GlcNAcß3Galß4Glcß1Cer, 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 Galß4GlcNAc in the core structure) were active in our assays, whereas gangliosides with lacto (Galß3GlcNAc) and ganglio (Galß3GalNAc) carbohydrate chains were not. Negative binding results were also obtained for disialylparagloboside (with terminal NeuAc8NeuAc) and NeuAc6-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.
1 To whom correspondence should be addressed; e-mail: halina.miller-podraza{at}medkem.gu.se
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