Synthesis of lipid A monosaccharide analogues containing acidic amino acid: exploring the structural basis for the endotoxic and antagonistic activities

Masao Akamatsu; Yukari Fujimoto; Mikayo Kataoka; Yasuo Suda; Shoichi Kusumoto; Koichi Fukase

doi:10.1016/j.bmc.2006.05.051

Synthesis of lipid A monosaccharide analogues containing acidic amino acid: exploring the structural basis for the endotoxic and antagonistic activities

Bioorg Med Chem. 2006 Oct 1;14(19):6759-77. doi: 10.1016/j.bmc.2006.05.051. Epub 2006 Jul 7.

Authors

Masao Akamatsu¹, Yukari Fujimoto, Mikayo Kataoka, Yasuo Suda, Shoichi Kusumoto, Koichi Fukase

Affiliation

¹ Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.

PMID: 16828560
DOI: 10.1016/j.bmc.2006.05.051

Abstract

For elucidation of the structural and conformational requirements on the endotoxic and antagonistic activity of lipid A derivatives, we designed and synthesized lipid A analogues containing acidic amino acid residues in place of the non-reducing end phosphorylated glucosamine. Definite switching of the endotoxic or antagonistic activity was observed depending on the difference of the acidic groups (phosphoric acid or carboxylic acid) in the lipid A analogues.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acylation
Amino Acids, Acidic / chemistry*
Amino Acids, Acidic / toxicity
Blood Cells / drug effects
Blood Cells / metabolism
Drug Design
Endotoxins / antagonists & inhibitors*
Endotoxins / chemistry*
Endotoxins / toxicity
Humans
In Vitro Techniques
Interleukin-6 / biosynthesis
Limulus Test
Lipid A / analogs & derivatives*
Lipid A / chemical synthesis*
Lipid A / toxicity
Lipopolysaccharides / pharmacology
Magnetic Resonance Spectroscopy
Structure-Activity Relationship

Substances

Amino Acids, Acidic
Endotoxins
Interleukin-6
Lipid A
Lipopolysaccharides