Molinaro Antonio, Holst Otto, Di Lorenzo Flaviana, Callaghan Maire, Nurisso Alessandra, D'Errico Gerardino, Zamyatina Alla, Peri Francesco, Berisio Rita, Jerala Roman, Jiménez-Barbero Jesús, Silipo Alba, Martín-Santamaría Sonsoles
Department of Chemical Sciences, University of Naples Federico II via Cinthia 4, 80126 Napoli (Italy).
Chemistry. 2015 Jan 7;21(2):500-19. doi: 10.1002/chem.201403923. Epub 2014 Oct 29.
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.
在许多革兰氏阴性菌中，脂多糖（LPS）及其脂质A部分对细菌的存活至关重要。脂质A根据其结构承载着LPS的毒性特性，并通过Toll样受体4/髓样分化因子2（TLR4/MD-2）受体复合物作为宿主先天免疫系统的强效激发剂。它常常引发各种各样的生物学效应，从显著增强抗感染能力到导致败血症和感染性休克的不受控制的大规模免疫反应。由于脂质A的生物活性受到其一级结构的强烈影响，脂质A衍生物的广泛化学合成对脂质A生物活性的表征做出了巨大贡献，为开发新的生物医学疗法提供了新的药理学靶点。在此，我们描述并讨论脂质A的化学方面及其在先天免疫中的作用，从（生物）合成、分离和表征到原子水平的分子识别。
