Lipid tetraacyl

On the other hand, Boons et al. demonstrated the synthesis of Rhizobium sin-1 lipid A derivatives [96, 97], E. coli hexaacylated and Salmonella typhimurium hep-taacylated lipid A [98], tetraacylated derivatives of lipid A from Porphyromonas gingivalis [99], and lipid A derivatives and KDO-linked lipid A of Neisseria meningitidis [100],... 

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... 

Lipid A was first synthesized by Imoto et al. in the mid 1980s [232,233], and the synthetic compound was found to possess all endotoxic activity of LPS. Many derivatives of Lipid A were subsequently synthesized in order to tease apart the importance of different structural elements for endotoxic activity. These investigations have been recently reviewed [234,235]. The tetraacylated lipid A precursor (lipid IVa, O Fig. 14) was found to compete with lipid A for binding to macrophages, but to have endotoxic activity 10 less than that of lipid A [235], with the result that it acts as a lipid A antagonist in human cells. In contrast, synthetic Re LPS (Kd02-lipid A, O Fig. 14) was found to have enhanced immunostimulatory ability compared with lipid A. 

Like other amphiphilic molecules, LPS aggregate and build up clusters in aqueous solutions. This process occurs only above a critical aggregate concentration (CAC) which has been established for a few lipids, but not, however, for LPS owing to extreme experimental difficulties. Estimations based on comparisons to values of other lipids led to the assumption of a CAC of < 10 M for hexaacyl-lipid A (O Fig. 16). For the lipid A precursor IVa (O Fig. 16) which represents a tetraacyl-lipid A, a CAC of < 10 has been reported [78]. 

The P configurations and solution-state conformations of a series of cis and trans-iu td perhydro-3,l,2-bezoxazaphosphinine 2-oxides have been studied by Kivela et by an extensive use of the experimental and DFT calculated /hp couplings. A detailed conformational analysis of a single molecule of the tetraacyl biosynthetic precursor-type lipid A and its characteristic supramolec-ular assembly in aqueous SDS-micelles has been performed by Oikawa et by the use of Thh and Thp couplings. 

Evidence to support the hypothesis that MsbA may be involved in lipid A transport is growing. htrB mutants accumulate tetraacylated lipid A in the inner membrane at the non-permissive temperature of 42 °C [41, 63). However, when mshA is provided in trans on a low copy plasmid, the tetraacylated lipid A is transported to the outer membrane [41]. In cells lacking mshA, hexaacylated lipid A accumulates in the inner membrane indicating that the transport of lipid A has been affected by the lack of mshA [41]. Taken together this strongly suggests that mshA plays a role in the movement of lipid A from the inner to the outer membrane, but direct biochemical assays remain to be developed. 

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