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Chemistry of Lipid A: At the Heart of Innate Immunity
Author(s) -
Molinaro Antonio,
Holst Otto,
Di Lorenzo Flaviana,
Callaghan Maire,
Nurisso Alessandra,
D'Errico Gerardino,
Zamyatina Alla,
Peri Francesco,
Berisio Rita,
Jerala Roman,
JiménezBarbero Jesús,
Silipo Alba,
MartínSantamaría Sonsoles
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201403923
Subject(s) - lipid a , innate immune system , lipopolysaccharide , tlr4 , immune system , toll like receptor , chemistry , immunity , pattern recognition receptor , biology , immunology
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.