Chemistry of Lipid A: At the Heart of Innate Immunity

被引：184

作者：

Molinaro, Antonio ^{[1
]}

Holst, Otto ^{[2
]}

Di Lorenzo, Flaviana ^{[1
]}

Callaghan, Maire ^{[3
]}

Nurisso, Alessandra ^{[4
]}

D'Errico, Gerardino ^{[1
]}

Zamyatina, Alla ^{[5
]}

Peri, Francesco ^{[6
]}

Berisio, Rita ^{[7
]}

Jerala, Roman ^{[8
]}

Jimenez-Barbero, Jesus ^{[9
]}

Silipo, Alba ^{[1
]}

Martin-Santamaria, Sonsoles ^{[9
,10
]}

机构：

[1] Univ Naples Federico II, Dept Chem Sci, I-80126 Naples, Italy

[2] Leibniz Ctr Med & Biosci, Res Ctr Borstel, Div Struct Biochem, D-23845 Borstel, Germany

[3] ITT Dublin, Dept Sci, CMHI, Dublin 24, Ireland

[4] Univ Lausanne, Univ Geneva, Sch Pharmaceut Sci, CH-1211 Geneva, Switzerland

[5] Univ Nat Resources & Life Sci, Dept Chem, A-1190 Vienna, Austria

[6] Univ Milano Bicocca, Dept Biotechnol & Biosci, I-20126 Milan, Italy

[7] CNR, Inst Biostruct & Bioimaging, I-80134 Naples, Italy

[8] Natl Inst Chem, Ljubljana, Slovenia

[9] CIB CSIC, Biol Res Ctr, Dept Chem & Phys Biol, Madrid 28040, Spain

[10] Univ CEU San Pablo, Fac Pharm, Dept Chem, Boadilla Del Monte 28668, Spain

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2015年 / 21卷 / 02期

基金：

奥地利科学基金会;

关键词：

innate immunity; lipid A; lipid A analogues; lipopolysaccharide; TLR4/MD-2; complex; UDP-N-ACETYLGLUCOSAMINE; ASSISTED-LASER-DESORPTION/IONIZATION; ESCHERICHIA-COLI ENCODES; ACYL-CHAIN SPECIFICITY; TOLL-LIKE RECEPTORS; BIOSYNTHETIC PRECURSOR; MASS-SPECTROMETRY; STRUCTURAL BASIS; CHEMICAL-CHARACTERIZATION; SALMONELLA-TYPHIMURIUM;

D O I：

10.1002/chem.201403923

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In many Gram-negative bacteria, lipopolysaccharide (LPS) and its lipid A moiety are pivotal for bacterial survival. Depending on its structure, lipid A carries the toxic properties of the LPS and acts as a potent elicitor of the host innate immune system via the Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD-2) receptor complex. It often causes a wide variety of biological effects ranging from a remarkable enhancement of the resistance to the infection to an uncontrolled and massive immune response resulting in sepsis and septic shock. Since the bioactivity of lipid A is strongly influenced by its primary structure, a broad range of chemical syntheses of lipid A derivatives have made an enormous contribution to the characterization of lipid A bioactivity, providing novel pharmacological targets for the development of new biomedical therapies. Here, we describe and discuss the chemical aspects regarding lipid A and its role in innate immunity, from the (bio)synthesis, isolation and characterization to the molecular recognition at the atomic level.

引用

页码：500 / 519

页数：20

共 208 条

[1] Synthesis and inhibitory activity of 8-substituted 2-deoxy-β-KDO against CMP-KDO synthetase [J].