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Studies of the binding activity of phage G13 to synthetic trisaccharides analogous to binding structures in Salmonella typhimurium and Escherichia coli C core saccharide. Correlation between conformation and binding activity

✍ Scribed by Gert W. Bruse; Ralfh Wollin; Stefan Oscarson; Per-Erik Jansson; Alf A. Lindberg


Publisher
John Wiley and Sons
Year
1991
Tongue
English
Weight
708 KB
Volume
4
Category
Article
ISSN
0952-3499

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✦ Synopsis


Abstract

Phage G13 binds to the carbohydrate part of lipopolysaccharides from rough mutants of Salmonella and Escherichia coli as the first event of infection. Equilibrium dialysis inhibition studies with native and synthetic trisaccharides as inhibitors suggested that phage G13 recognizes branched oligosaccharides having 6‐O‐α‐ or 7‐O‐α‐glycosyl groups with α‐Man(1→3) [α‐Man(1→6)]Man (Man[Man]Man) and α‐Glc(1→3)‐[α‐Hep(1→7)α‐Hep(1→3)α‐Hep(1→5) Kdo as the smallsest saccharides with inhibitory activity (Wollin et. al., 1989). Of four synthetic analogues to Man[Man]Man only Man(1→3)[α‐Gal(1→6)]α‐Man‐Ome (Man[Gal]‐Man) and α‐Glc(1→3)]α‐Hep(1→7)α‐Hep‐Ome (Glc[Hep]Hep) inhibited the binding of labelled E. coli. C core nonasaccharide ligand to G13 with activities which were 10‐ and 15‐fold lower than Man[Man]Man. The trisaccharides α‐Man(2→3)[α‐Glc(1→6)]α‐Man‐OMe (Man[Glc]Man) and α‐Man(1→3)[α‐Tal(1→6)]α‐Man‐OMe (Man[Tal]Man) showed no inhibition at concentrations 75‐fold higher than Man[Man]Man. Minimum energy conformation calculations of the saccharides using the GESA method showed that the 6‐O‐α‐Man group in Man[Man]Man and the 7‐O‐α‐Hep group in SL805 pentasaccharide expose their OH‐2 and OH‐3 groups in a similar way and these are postulated to be key structural features for binding activity. The importance of hydroxy groups at certain positions is implied from the fact that both manno‐ and galacto‐isomers are active. We also conclude that the O6‐C6‐C5‐O5‐C1 region of the 3‐O‐α‐glycosyl group in the Man[Man]Man trisaccharide, or part of it, is important for the G13 binding activity.