Lipopolysaccharide (LPS) located in the outer leaflet of the bacterial cell membrane constitutes a biomedically relevant target to overcome antibiotic resistance of numerous Gram-negative strains. In order to study binding interactions of the structurally conserved enterobacterial inner core with antibodies and lectins in molecular detail, we have set out to synthesize phosphorylated heptose inner core LPS ligands. By utilizing an orthogonal protecting group pattern with early introduction of a phosphate group at O-4, chain extension by additional carbohydrate substituents at O-3 and O-7 of a central heptose moiety, respectively, has been achieved in a highly convergent approach. Crystallographic studies of the heptose ligands with human lung surfactant protein D (SP-D) and Burkholderia cenocepacia lectins Bc2L-A and Bc2L-C  revealed major interactions - mediated by calcium ions  - towards ring and side chain hydroxyl functions as well as phosphate substituents of the heptose core.

Synthesis and lectin binding of phosphorylated L-glycero-D-manno-heptose LPS ligands

245th National Meeting (2013)

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