Chemistry of Lipid A: At the Heart of Innate Immunity |
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| Authors: | Prof Antonio Molinaro Prof Otto Holst Dr Flaviana Di?Lorenzo Dr Maire Callaghan Dr Alessandra Nurisso Dr Gerardino D'Errico Dr Alla Zamyatina Prof Francesco Peri Dr Rita Berisio Prof Roman Jerala Prof Jesús Jiménez‐Barbero Dr Alba Silipo Prof Sonsoles Martín‐Santamaría |
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| Institution: | 1. Department of Chemical Sciences, University of Naples Federico II via Cinthia 4, 80126 Napoli (Italy);2. Division of Structural Biochemistry, Research Center Borstel, Leibniz‐Center for Medicine and Biosciences, Parkallee 4a/c, 23845 Borstel (Germany);3. Centre of Microbial Host Interactions (CMHI), Department of Science, ITT‐Dublin, Dublin 24 (Ireland);4. School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30, Quai Ernest‐Ansermet, 1211 Geneva (Switzerland);5. Department of Chemistry, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna (Austria);6. Department of Biotechnology and Biosciences, University of Milano‐Bicocca, Piazza della Scienza 2, 20126 Milano (Italy);7. Institute of Biostructures and Bioimaging, National Research Council, Via Mezzocannone 16, 80134 Naples (Italy);8. National Institute of Chemistry, Hajdrihova 19, Ljubljana (Slovenia);9. Department of Chemical and Physical Biology, Centre for Biological Research, CIB‐CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain);10. Department of Chemistry, Faculty of Pharmacy, Universidad CEU San Pablo, Urbanizacion Monteprincipe, 28668‐Boadilla del Monte (Spain) |
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| 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. |
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| Keywords: | innate immunity lipid A lipid A analogues lipopolysaccharide TLR4/MD‐2 complex |
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