The influence of the long chain fatty acid on the antagonistic activities of Rhizobium sin-1 lipid A

Yanghui Zhang; Margreet A. Wolfert; Geert-Jan Boons

doi:10.1016/j.bmc.2007.05.012

The influence of the long chain fatty acid on the antagonistic activities of Rhizobium sin-1 lipid A

Yanghui Zhang, Margreet A. Wolfert, Geert-Jan Boons

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The lipid A from nitrogen-fixing bacterial species Rhizobium sin-1 is structurally unusual due to lack of phosphates and the presence of a 2-aminogluconolactone and a very long chain fatty acid, 27-hydroxyoctacosanoic acid (27OHC28:0), moiety. This structurally unusual lipid A can antagonize TNF-α production by human monocytes induced by Escherichia coli LPS. To establish the relevance of the unusual long chain 27-hydroxyoctacosanoic acid for antagonistic properties, a highly convergent strategy for the synthesis of several derivatives of the lipid A of R. sin-1 has been developed. Compound 1 is a natural R. sin-1 lipid A having a 27-hydroxyoctacosanoic acid at C-2′, compound 2 contains an octacosanoic acid moiety at this position, and compound 3 is modified by a short chain tetradecanoic acid. Cellular activation studies with a human monocytic cell line have shown that the octacosanoic acid is important for optimal antagonistic properties. The hydroxyl of the natural 27-hydroxyoctacosanoic moiety does, however, not account for inhibitory activity. The resulting structure-activity relationships are important for the design of compounds for the treatment of septic shock. © 2007 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	4800-4812
Number of pages	13
Journal	Bioorganic and Medicinal Chemistry
Volume	15
Issue number	14
DOIs	https://doi.org/10.1016/j.bmc.2007.05.012
Publication status	Published - 15 Jul 2007
Externally published	Yes

Keywords

Antagonist
Lipid A
Lipopolysaccharides
Septic shock
Tumor necrosis factor
2 deoxy 6 o [2 deoxy 3 (3 hydroxytetradecanoyl) 2 [3 (27 hydroxyoctacosanoyloxy)hexadecanoylamino] beta dextro glucopyranosyl] 2 (3 hydroxyhexadecanoylamino) 3 o (3 hydroxyhexadecanoyl) dextro glucono 1,5 lactone
2 deoxy 6 o [2 deoxy 3 o (3 hydroxyhexadecanoyl) 2 (3 tetradecanoyloxyhexadecanoylamino) beta dextro glucopyranosyl] 2 (3 hydroxyhexadecanoylamino) 3 o (3 hydroxyhexadecanoyl) dextro glucono 1,5 lactone
2 deoxy 6 o [2 deoxy 3 o (3 hydroxytetradecanoyl) 2 (3 octacosanoyloxyhexadecanoylamino) beta dextro glucopyranosyl] 2 (3 hydroxyhexadecanoylamino) 3 o (3 hydroxyhexadecanoyl) dextro glucono 1,5 lactone
Escherichia coli lipopolysaccharide
lactone derivative
lipid A
long chain fatty acid
unclassified drug
article
bacterial strain
cell activation
drug synthesis
Escherichia coli
human
human cell
monocyte
Rhizobium
septic shock
structure activity relation

Access to Document

10.1016/j.bmc.2007.05.012

Cite this

@article{739ff0cbc314463080cd394b6f30e193,

title = "The influence of the long chain fatty acid on the antagonistic activities of Rhizobium sin-1 lipid A",

abstract = "The lipid A from nitrogen-fixing bacterial species Rhizobium sin-1 is structurally unusual due to lack of phosphates and the presence of a 2-aminogluconolactone and a very long chain fatty acid, 27-hydroxyoctacosanoic acid (27OHC28:0), moiety. This structurally unusual lipid A can antagonize TNF-α production by human monocytes induced by Escherichia coli LPS. To establish the relevance of the unusual long chain 27-hydroxyoctacosanoic acid for antagonistic properties, a highly convergent strategy for the synthesis of several derivatives of the lipid A of R. sin-1 has been developed. Compound 1 is a natural R. sin-1 lipid A having a 27-hydroxyoctacosanoic acid at C-2′, compound 2 contains an octacosanoic acid moiety at this position, and compound 3 is modified by a short chain tetradecanoic acid. Cellular activation studies with a human monocytic cell line have shown that the octacosanoic acid is important for optimal antagonistic properties. The hydroxyl of the natural 27-hydroxyoctacosanoic moiety does, however, not account for inhibitory activity. The resulting structure-activity relationships are important for the design of compounds for the treatment of septic shock. {\textcopyright} 2007 Elsevier Ltd. All rights reserved.",

keywords = "Antagonist, Lipid A, Lipopolysaccharides, Septic shock, Tumor necrosis factor, 2 deoxy 6 o [2 deoxy 3 (3 hydroxytetradecanoyl) 2 [3 (27 hydroxyoctacosanoyloxy)hexadecanoylamino] beta dextro glucopyranosyl] 2 (3 hydroxyhexadecanoylamino) 3 o (3 hydroxyhexadecanoyl) dextro glucono 1,5 lactone, 2 deoxy 6 o [2 deoxy 3 o (3 hydroxyhexadecanoyl) 2 (3 tetradecanoyloxyhexadecanoylamino) beta dextro glucopyranosyl] 2 (3 hydroxyhexadecanoylamino) 3 o (3 hydroxyhexadecanoyl) dextro glucono 1,5 lactone, 2 deoxy 6 o [2 deoxy 3 o (3 hydroxytetradecanoyl) 2 (3 octacosanoyloxyhexadecanoylamino) beta dextro glucopyranosyl] 2 (3 hydroxyhexadecanoylamino) 3 o (3 hydroxyhexadecanoyl) dextro glucono 1,5 lactone, Escherichia coli lipopolysaccharide, lactone derivative, lipid A, long chain fatty acid, unclassified drug, article, bacterial strain, cell activation, drug synthesis, Escherichia coli, human, human cell, monocyte, Rhizobium, septic shock, structure activity relation",

author = "Yanghui Zhang and Wolfert, {Margreet A.} and Geert-Jan Boons",

year = "2007",

month = jul,

day = "15",

doi = "10.1016/j.bmc.2007.05.012",

language = "English",

volume = "15",

pages = "4800--4812",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd",

number = "14",

}

TY - JOUR

T1 - The influence of the long chain fatty acid on the antagonistic activities of Rhizobium sin-1 lipid A

AU - Zhang, Yanghui

AU - Wolfert, Margreet A.

AU - Boons, Geert-Jan

PY - 2007/7/15

Y1 - 2007/7/15

N2 - The lipid A from nitrogen-fixing bacterial species Rhizobium sin-1 is structurally unusual due to lack of phosphates and the presence of a 2-aminogluconolactone and a very long chain fatty acid, 27-hydroxyoctacosanoic acid (27OHC28:0), moiety. This structurally unusual lipid A can antagonize TNF-α production by human monocytes induced by Escherichia coli LPS. To establish the relevance of the unusual long chain 27-hydroxyoctacosanoic acid for antagonistic properties, a highly convergent strategy for the synthesis of several derivatives of the lipid A of R. sin-1 has been developed. Compound 1 is a natural R. sin-1 lipid A having a 27-hydroxyoctacosanoic acid at C-2′, compound 2 contains an octacosanoic acid moiety at this position, and compound 3 is modified by a short chain tetradecanoic acid. Cellular activation studies with a human monocytic cell line have shown that the octacosanoic acid is important for optimal antagonistic properties. The hydroxyl of the natural 27-hydroxyoctacosanoic moiety does, however, not account for inhibitory activity. The resulting structure-activity relationships are important for the design of compounds for the treatment of septic shock. © 2007 Elsevier Ltd. All rights reserved.

AB - The lipid A from nitrogen-fixing bacterial species Rhizobium sin-1 is structurally unusual due to lack of phosphates and the presence of a 2-aminogluconolactone and a very long chain fatty acid, 27-hydroxyoctacosanoic acid (27OHC28:0), moiety. This structurally unusual lipid A can antagonize TNF-α production by human monocytes induced by Escherichia coli LPS. To establish the relevance of the unusual long chain 27-hydroxyoctacosanoic acid for antagonistic properties, a highly convergent strategy for the synthesis of several derivatives of the lipid A of R. sin-1 has been developed. Compound 1 is a natural R. sin-1 lipid A having a 27-hydroxyoctacosanoic acid at C-2′, compound 2 contains an octacosanoic acid moiety at this position, and compound 3 is modified by a short chain tetradecanoic acid. Cellular activation studies with a human monocytic cell line have shown that the octacosanoic acid is important for optimal antagonistic properties. The hydroxyl of the natural 27-hydroxyoctacosanoic moiety does, however, not account for inhibitory activity. The resulting structure-activity relationships are important for the design of compounds for the treatment of septic shock. © 2007 Elsevier Ltd. All rights reserved.

KW - Antagonist

KW - Lipid A

KW - Lipopolysaccharides

KW - Septic shock

KW - Tumor necrosis factor

KW - 2 deoxy 6 o [2 deoxy 3 (3 hydroxytetradecanoyl) 2 [3 (27 hydroxyoctacosanoyloxy)hexadecanoylamino] beta dextro glucopyranosyl] 2 (3 hydroxyhexadecanoylamino) 3 o (3 hydroxyhexadecanoyl) dextro glucono 1,5 lactone

KW - 2 deoxy 6 o [2 deoxy 3 o (3 hydroxyhexadecanoyl) 2 (3 tetradecanoyloxyhexadecanoylamino) beta dextro glucopyranosyl] 2 (3 hydroxyhexadecanoylamino) 3 o (3 hydroxyhexadecanoyl) dextro glucono 1,5 lactone

KW - 2 deoxy 6 o [2 deoxy 3 o (3 hydroxytetradecanoyl) 2 (3 octacosanoyloxyhexadecanoylamino) beta dextro glucopyranosyl] 2 (3 hydroxyhexadecanoylamino) 3 o (3 hydroxyhexadecanoyl) dextro glucono 1,5 lactone

KW - Escherichia coli lipopolysaccharide

KW - lactone derivative

KW - lipid A

KW - long chain fatty acid

KW - unclassified drug

KW - article

KW - bacterial strain

KW - cell activation

KW - drug synthesis

KW - Escherichia coli

KW - human

KW - human cell

KW - monocyte

KW - Rhizobium

KW - septic shock

KW - structure activity relation

U2 - 10.1016/j.bmc.2007.05.012

DO - 10.1016/j.bmc.2007.05.012

M3 - Article

SN - 0968-0896

VL - 15

SP - 4800

EP - 4812

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 14

ER -

The influence of the long chain fatty acid on the antagonistic activities of Rhizobium sin-1 lipid A

Abstract

Keywords

Access to Document

Fingerprint

Cite this