86559-73-1

Usage

Uses

Used in Pharmaceutical Industry:
Lipid X is used as an immunostimulant for its ability to enhance the immune response against infections, particularly those caused by gram-negative organisms. Its immunostimulatory properties make it a valuable agent in the development of treatments for severe infections.
Used in Endotoxin Protection:
Lipid X is used as an anti-endotoxin agent for its capacity to protect against the harmful effects of endotoxins, which are toxic substances released by gram-negative bacteria. This protective effect has been demonstrated in both mice and sheep, highlighting its potential as a therapeutic agent in the prevention and treatment of endotoxin-related complications.
Used in Severe Infection Treatment:
Lipid X is used as a novel agent to enhance survival in animal models of severe infection with gram-negative organisms. Its ability to stimulate the immune system and protect against endotoxins makes it a promising candidate for the development of treatments aimed at improving outcomes in patients with severe infections caused by gram-negative bacteria.

InChI:InChI=1/C34H66NO12P/c1-3-5-7-9-11-13-15-17-19-21-26(37)23-29(39)35-31-33(32(41)28(25-36)45-34(31)47-48(42,43)44)46-30(40)24-27(38)22-20-18-16-14-12-10-8-6-4-2/h26-28,31-34,36-38,41H,3-25H2,1-2H3,(H,35,39)(H2,42,43,44)/t26-,27-,28-,31-,32-,33-,34-/m1/s1

Upstream product

• 87357-67-3 (R)-3-benzyloxytetradecanoic acid 
• 72333-25-6 allyl 3,4,6-tri-O-acetyl-2-(chloroacetamido)-2-deoxy-β-D-glucopyranoside 
• 93390-33-1 (R)-3-Benzyloxy-tetradecanoic acid (2R,3R,4R,5S,6R)-2-allyloxy-5-benzyloxy-6-benzyloxymethyl-3-((R)-3-benzyloxy-tetradecanoylamino)-tetrahydro-pyran-4-yl ester 
• 93390-34-2 (R)-3-Benzyloxy-tetradecanoic acid (2R,3S,4R,5R,6S)-3-benzyloxy-2-benzyloxymethyl-5-((R)-3-benzyloxy-tetradecanoylamino)-6-hydroxy-tetrahydro-pyran-4-yl ester 
• 93390-32-0 (2R,3R,4R,5S,6R)-2-Allyloxy-3-amino-5-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-4-ol 
• 99519-07-0 allyl 2-<(R)-3-benzyloxytetradecanamido>-3-O-<(R)-3-benzloxytetradecanoyl>-2-deoxy-4,6-isopropylidene-β-D-glucopyranoside 
• 99519-04-7 allyl 2-chloroacetamido-2-deoxy-4,6-isopropylidene-β-D-glucopyranoside 
• 99519-03-6 allyl 2-chloroacetamido-2-deoxy-β-D-glucopyranoside 
• 99519-05-8 Allyl 2-amino-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside 
• 111789-77-6 4,6-O-benzylidene-2-<(R)-3-benzyloxytetradecanamido>-2-deoxy-D-glucopyranose 
• 109304-43-0 4,6-O-benzylidene-2-<(R)-3-benzyloxytetradecanamido>-2-deoxy-α-D-glucopyranose 1-(dibenzyl phosphate) 
• 101649-06-3 N-((R)-3-Benzyloxytetradecanoyloxy)succinimid 
• 111789-76-5 2-<(R)-3-benzyloxytetradecanamido>-2-deoxy-D-glucopyranose 
• 112159-08-7 (R)-3-Benzyloxy-tetradecanoic acid (4aR,6R,7R,8R,8aS)-7-((R)-3-benzyloxy-tetradecanoylamino)-6-(bis-benzyloxy-phosphoryloxy)-2,2-dimethyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-yl ester 

Relevant academic research and scientific papers

The substrate-binding cap of the UDP-diacylglucosamine pyrophosphatase LpxH is highly flexible, enabling facile substrate binding and product release

Gram-negative bacteria are surrounded by a secondary membrane of which the outer leaflet is composed of the glycolipid lipopolysaccharide (LPS), which guards against hydrophobic toxins, including many antibiotics. Therefore, LPS synthesis in bacteria is an attractive target for antibiotic development. LpxH is a pyrophosphatase involved in LPS synthesis, and previous structures revealed that LpxH has a helical cap that binds its lipid substrates. Here, crystallography and hydrogen– deuterium exchange MS provided evidence for a highly flexible substrate-binding cap in LpxH. Furthermore, molecular dynamics simulations disclosed how the helices of the cap may open to allow substrate entry. The predicted opening mechanism was supported by activity assays of LpxH variants. Finally, we confirmed biochemically that LpxH is inhibited by a previously identified antibacterial compound, determined the potency of this inhibitor, and modeled its binding mode in the LpxH active site. In summary, our work provides evidence that the substrate-binding cap of LpxH is highly dynamic, thus allowing for facile substrate binding and product release between the capping helices. Our results also pave the way for the rational design of more potent LpxH inhibitors.

An alternative route for UDP-diacylglucosamine hydrolysis in bacterial lipid a biosynthesis

The outer leaflet of the outer membranes of Gram-negative bacteria is composed primarily of lipid A, the hydrophobic anchor of lipopolysaccharide. Like Escherichia coli, most Gram-negative bacteria encode one copy of each of the nine genes required for lipid A biosynthesis. An important exception exists in the case of the fourth enzyme, LpxH, a peripheral membrane protein that hydrolyzes UDP-2,3-diacylglucosamine to form 2,3-diacylglucosamine 1-phosphate and UMP by catalyzing the attack of water at the α-P atom. Many Gram-negative organisms, including all α-proteobacteria and diverse environmental isolates, lack LpxH. Here, we report a distinct UDP-2,3-diacylglucosamine pyrophosphatase, designated LpxI, which has no sequence similarity to LpxH but generates the same products by a different route. LpxI was identified because its structural gene is located between lpxA and lpxB in Caulobacter crescentus. The lpxI gene rescues the conditional lethality of lpxH-deficient E. coli. Lysates of E. coli in which C. crescentus LpxI (CcLpxI) is overexpressed display high levels of UDP-2,3-diacylglucosamine pyrophosphatase activity. CcLpxI was purified to >90% homogeneity. CcLpxI is stimulated by divalent cations and is inhibited by EDTA. Unlike E. coli LpxH, CcLpxI is not inhibited by an increase in the concentration of detergent, and its pH dependency is different. When the CcLpxI reaction is conducted in the presence of H218O, the 18O is incorporated exclusively into the 2,3-diacylglucosamine 1-phosphate product, as judged by mass spectrometry, demonstrating that CcLpxI catalyzes the attack of water on the β-P atom of UDP-2,3-diacylglucosamine.

A CONVENIENT SYNTHESIS OF 2-DEOXY-2--3-O--α-D-GLUCOPYRANOSE 1-PHOSPHATE (LIPID X)

The crystalline tris(hydroxymethyl)aminomethane ("Tris") salt of 2-deoxy-2--3-O--α-D-glucopyranose 1 phosphate (lipid X) has been synthesised from 2-amino-2-deoxy-D-glucose hydrochloride in five st

CHEMICAL SYNTHESES OF LIPID X AND LIPID Y, ACYL GLUCOSAMINE 1-PHOSPHATES ISOLATED FROM ESCHERICHIA COLI MUTANTS

Two new phospholipids, 2-N; 3-O-bis(R) -3-hydroxytetradecanoylglucosamine 1-phosphate and 2-N-(R)-3-hexadecenoyloxytetradecanoyl-3-O-(R)-3-hydroxytetradecenoylglucosamine 1-phosphate, were synthesized and identified with natural lipid X and lipid Y respec