Primary Structure of Lipid A Backbone, Polar Substituents, and Fatty Acids

Primary Structure of Lipid A Backbone, Polar Substituents, and Fatty Acids 

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 

As these results and Fig. 2 show, three structural components may be defined in lipid A (/) the lipid A backbone consisting of a pyranosidic HexN disaccharide and phosphate groups, (ii) substituents of the backbone phosphate residues (polar head groups), and (iii) fatty acids. Therefore, lipid A of different bacteria may be classified according to the nature of the backbone constituents (GlcpN or GlcpN3N), the type and nature of the polar head groups, and features of the acylation pattern. In a few instances, other backbone substituents have been encountered. These will be described later in conjunction with individual lipid A forms. 

A disadvantage of the derivatization procedure used in the case of S. typhimurium (60) was that the trimethylsilylated dimethyl monophosphoryl lipid A derivative was not suitable for the characterization of the (free) hydroxyl group in position 4. This identification could be achieved, however, by the approach of Imoto et al. (35), who investigated the dimethyl monophosphoryl lipid A of E. coli and its per-O-acetylated derivative to compare the chemical shifts before and after acetylation. From the differences in the chemical shift observed in H-n.m.r., the authors could clearly demonstrate that, in their preparation, position 4 of GlcN(I) was free. All 

The first 13C-n.m.r. analysis of the / -(l — 6) Glc/ N disaccharide was carried out on the lipid A backbone of E. coli (61). However, the assignments in this study were different from those obtained by Krasikova et al. (62) who synthesized the disaccharide / -D-GlcpN-( 1 — 6)-D-GlcpN and used it as a reference compound. 13C-N.m.r. was also used to identify the lipid A backbone of S. typhimurium (63), S. minnesota (64,64a), E. coli (34,64a, 65,66,66a), Proteus mirabilis (67), and Haemophilus influenzae (68). 

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