Phosphorylated disaccharides structure

Leishmaniasis is a disease that affects over 12 million people worldwide. One of the carbohydrates that is exposed on the Leishmania parasite surface is a structure consisting of a glycosylphosphatidylinositol (GPl) anchor, a repeating phosphorylated disaccharide and tetrasaccharide cap 14. The tetrasaccharide cap was synthesized by automation [38] using three building blocks (Scheme 9). 

The structural components encountered in E. coli are also present in lipid A of other bacterial sources. Thus, a survey of the structures analyzed shows that lipid A, in general, contain two g/wcoconfigured and pyranosidic D-hexosamine residues (2-amino-2-deoxy-D-glucose, GlcpN, or 2,3-diamino-2,3-dideoxy-D-glucose, GlcpN3N, also termed DAG (49,50)], which are present as a ) -(l — 6)-linked disaccharide (monosaccharide backbones have also been identified, but the respective lipid A lack endotoxic activity). The disaccharide is phosphorylated by one or, in most cases, two phosphate... 

The structural principle identified in many lipid A s as the hydrophilic backbone, a phosphorylated B(1— 6)-linked D-glucosa-minyl disaccharide, is present in closely related and taxonomi-cally remote groups of bacteria. Therefore it represents an ubiquitous and common component of lipid A s from various Gram-negative bacteria. A D-glucosaminyl disaccharide being B(1— 6)-linked has, to our knowledge, not been found in other natural substances. Hence, this structure is unique and characteristic for Lipid A. 

Employing the same strategy and precursors as outlined above (Sects. 2.3 and 4), the phosphorylated heptoside disaccharides 38-40 [10] (Fig. 4), corresponding to Salmonella core structures (Fig. 1), were synthesised. A 7-0-phosphorylated structure (41) of the same disaccharide, corresponding to a Neisseria structure, has also been synthesised by van Boom [11]. This derivative was synthesised as the ethanolamine phosphate derivative and the oligosaccharide part was linked via a spacer to a peptide part, altogether re-... 

Fig. 4. Structures of synthesised phosphorylated heptose-containing disaccharides...

Figure 8.8. MD-models of phosphorylated high-mannose M7 and a glycopeptide mimic, as seen trom the point of view of the mannose 6-phosphate receptor. Disaccharide phosphates are emphasized as spheres. The structure of the mimic was obtained after 40 ps at 400 K and 10 ps at 300 K using the Insight/Discov-er program package.

Treatment of the lipopolysaccharide of a mutant of Escherichia coli, containing no hcptose, with alkali released two phosphorylated components, LPS I and II, both consisting of a substituted 2-amino-2-deoxy-D-glucosyl disaccharide, but differing in the nature of the phosphate groups present at the glycosyl position. Their structures (3) were determined. LPS I contained two phospho-... 

Figure 1. Chemical structures of lipid A-diphosphate (A) and two antagonistic lipid A-diphosphate molecules, (B and C). Lipid A-diphosphate from E. coli is a 1,4-di-phosphorylated P-1,6-linked D-glucosamine disaccharide with four residues of amide-and esterified R-(-)-3-hydroxy fatty acids ( denotes the chiral centers in the hydroxy fatty-acid esters, apart form the chiral and epimeric carbons in the disaccharide moieties which are not marked). The antagonistic lipid A-diphosphate molecules shown in (B) and (C) contain the same disaccharide as in (A) however, they differ in the number anchored carbohydrate positions and the number of chiral fatty-acid chains but the chain lengths is the same (C J. The corresponding monophosphate of lipid A is only phosphorylated at the reducing end of the disaccharide.

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