title: Chemistry of lipid A: at the heart of innate immunity.
abstract: 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.
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II via Cinthia 4, 80126 Napoli (Italy). molinaro@unina.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinaro
authors.forename: Otto
authors.initials: O
authors.lastname: Holst
authors.forename: Flaviana
authors.initials: F
authors.lastname: Di Lorenzo
authors.forename: Maire
authors.initials: M
authors.lastname: Callaghan
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nurisso
authors.forename: Gerardino
authors.initials: G
authors.lastname: D'Errico
authors.forename: Alla
authors.initials: A
authors.lastname: Zamyatina
authors.forename: Francesco
authors.initials: F
authors.lastname: Peri
authors.forename: Rita
authors.initials: R
authors.lastname: Berisio
authors.forename: Roman
authors.initials: R
authors.lastname: Jerala
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.forename: Alba
authors.initials: A
authors.lastname: Silipo
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Martín-Santamaría
mesh_terms: D000818:Animals; D006090:Gram-Negative Bacteria / Q000737:chemistry* / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D008050:Lipid A / Q000031:analogs & derivatives / Q000737:chemistry* / Q000276:immunology*; D051218:Lymphocyte Antigen 96 / Q000276:immunology; D008958:Models, Molecular; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: C495377:LY96 protein, human; D008050:Lipid A; D051218:Lymphocyte Antigen 96; D051197:Toll-Like Receptor 4
keywords: TLR4/MD-2 complex; innate immunity; lipid A; lipid A analogues; lipopolysaccharide