101649-06-3Relevant articles and documents
Synthesis and in vitro activities of a spacer-containing glycophospholipid ligand of a lipopolysaccharide receptor involved in endotoxin tolerance
Charon, Daniel,Mondange, Michelle,Pons, Jean-Francois,Le Blay, Karine,Chaby, Richard
, p. 755 - 765 (2007/10/03)
A glycophospholipid consisting in a derivative of N,N'-acylated and bisphosphorylated 2,3-dideoxy-2,3-diamino-d-glucose, bearing a 6-aminocaproyl side chain as spacer arm at carbon 6 (PPDm2-B), has been synthesized and its effect on murine macrophages evaluated. The synthesis started from 2,3-diamino-d-glucose, which was best obtained from glucosamine essentially by known procedures, since attempts to use another known precursor (3-nitro-glycoside) led to unexpected results. Selective N-acylation was performed with the hydroxysuccinimide ester of (d)-3-benzyloxymyritic acid followed by esterification of the sole primary hydroxyl function by 6-azidocaproylchloride and phosphorylation of the resulting 1,4-diol by treatment with tetrabenzyl pyrophosphate. Hydrogenation on a Pd on carbon catalyst permitted the isolation of 6-(6-aminohexanoyl)-2,3-dideoxy-2,3-di-[(R)-3-hydroxy-tetradecanamido]-α-d-glucopyranose 1,4-diphosphate (PPDm2-B). In mouse macrophages, PPDm2-B enhanced the lipopolysaccharide (LPS)-dependent secretion of tumor necrosis factor alpha (TNF-α), and inhibited the LPS-induced desensitization of these cells. The data suggest that PPDm2-B interacts in a serum-independent way with an LPS receptor different from CD14, and involved in endotoxin tolerance. Binding studies of a fluorescent derivative of PPDm2-B indicated that the expression of this unknown receptor is down-regulated during in vitro culture of the cells. Owing to its spacer arm, PPDm2-B could thus be a promising tool for future studies of this receptor. Copyright (C) 1998 Elsevier Science Ltd.
