Lipid A Analogues

5 Lipid A Analogues. - Of a set of eleven new JV-acylated L-serine-containing 2-amino-2-deoxy-D-glucose derivatives synthesized as Lipid A analogues and evaluated as synthetic immunoadjuvants, compound 78 had the greatest 

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A number of lipid A analogues that have been synthesized by Shiba and Kusumoto and their collegues in Osaka (for details see the following article by Shiba et al.) have been tested in Freiburg for biological... 

Figure 4. Biological activities of synthetic lipid A analogues. The designations of the preparations are as in Chapter 11.

Yasuda, T., Kanegasaki, Sh.f Tsumita, T., Tadakuma, T., Homma, 3.Y., Inage, M., Kusumoto, S., and Shiba, T. (1982). Biological activity of chemically synthesized lipid A analogues. Demonstration of adjuvant effect in hapten-sensitized liposomal system. Eur. 3. Biochem., 124, 405-007... 

Brandenburg, K., Kusumoto, S., Seydel U. Conformational studies of synthetic lipid A analogues and partial structures by infrared spectroscopy. Biochim Biophys Acta 1329 (1997) 193-201. 

Jiang, Z.H., Budzynski, W.A., Qiu, D., Yalamati, D., Koganty, R.R. Monophosphoryl lipid A analogues with varying 3-O-substitution Synthesis and potent adjuvant activity. Carbohydr Res 342 (2007) 784-796. 

Kumar, A., Bunnell, E., Lynn, M., Anel, R., Habet, K., Neumann, A., Parrillo, J.E. Experimental human endotoxemia is associated with depression of load-independent contractility indices Prevention by the lipid a analogue E5531. Chest 126 (2004) 860-867. 

A library of acidic amino-acid-substituted monosaccharide lipid A analogues was also prepared for elucidation of the stmctural basis to biological function [131]. The library of lipid A analogues was also used for the crystallization of the coreceptor Md-2, which constitutes the receptor complex with Toll-like receptor 4 (TLR4). The antagonistic tetraacylated lipid A (the... 

Synthetic lipid A analogues were used in FTTR investigations to study possible intermolecular conformations of neighboring molecules [79]. There is good evidence that the bisphosphory-lated /3-(l—>6)-linked GlcN disaccharide backbone of lipid A is inclined (20—40° relative to the membrane normal), thus, the phosphate linked to 01 is reaching to the outside and that at 04 is buried in the membrane. This model is supported by data from transition temperature measurements and calorimetric experiments. However, it should be noted that other authors reported the reverse conformation with the 04 phosphate on the surface and the 01 phosphate in the membrane [80,81]. 

Phosphorylated lipophilic derivatives of ara C as potential pro-drugs, spin-labelled ATP derivatives and phosphorylation products of 5 -AMP are referred to in Chapter 20, inositol phosphate derivatives in Chapter 18, and H-labelled Lipid A analogues in Chapter 3. Analogues of 2-deoxy-D-ribose with phosphorous in the ring are covered in Chapter 17. 

A review of the isolation and separation of phosphatldes and glyco-lipids, by solvent fractionation, preparative column chromatography, and h.p.l.c., has appeared. Lipid X (16) and Lipid Y (17)> rel-ated to lipid A and found in E. coli mutants, have been synthesized. Biologically active monosaccharide Lipid A analogues (18) have been synthesized from the appropriate I -substituted butyl glucosaminide. Reference is made to tri- and tetrasaccharide pyrophosphate esters, intermediates in N-glycoprotein biosynthesis. 

Two reviews of the total synthesis and biological activity of lipid A analogues have appeared. These and other references to glucosamine-based disaccharides are discussed in Chapter 7-... 

Japanese workers have reported extensively on the synthesis of lipid A analogues, which contain l-0-phosphoryl-2-amino-2-deoxy-D-glucose units N-acylated with fatty acids, 3-hydroxy- or 3-(fatty acyloxy)-fatty acid moieties. This work is covered in detail in Chapter 7, and to lesser extent in Chapter 3. N-Acyl derivatives of methyl 2-amino-2-deoxy-a-D-galactopyranoside have been synthesized conventionally from the free amine, in connection with... 

The synthesis and immunological properties of MDP (N-acetyl-muramoyl-L-alanyl-D-isoglutcunine) and bacterial lipid A analogues continue to attract considerable attention. A large scale ... 

The Lipid A analogues (84) - (88) have been synthesized. The 4,6-disulphated 1-thyminyl-analogue (85) had anti-HIV activity, while the analogues (86) and (87), in which the natural a-glycosyl phosphate moiety is substituted by a phosphono-oigrethyl group, had anti-tumour activity. ... 

A new method of synthesising 1,6-1inked compounds affords products with ca 70% efficiency (Scheme 15). The mutagenicity and lethal toxicity of chemically synthesised lipid A analogues having 2,3-acyloxyacylglucosamine 4-phosphate with... 

The fluoroacid (122), required for incorporation into Lipid A analogues, has been prepared from tri-O-acetyl-D-glucal (sugar carbons numbered). ... 

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