Progress in the synthesis and biological evaluation of lipid A and its derivatives.

Abstract

Lipid A is one of the core structures of bacterial lipopolysaccharides (LPSs), and it is mainly responsible for the strong immunostimulatory activities of LPS through interactions with the Toll-like receptors and other molecules in the human immune system. To obtain structurally homogeneous and well-defined lipid As and its derivatives in quantities meaningful for various biological studies and applications, their chemical synthesis has become a focal point. This review has provided a survey of significant progresses made in the synthesis of lipid A, and its derivatives that carry diverse saturated and unsaturated lipids, have the phosphate group at its reducing end replaced with a more stable phosphate or carboxyl group, or lack the reducing end phosphate or both phosphate groups, as well as progresses in the synthesis of LPS analogs and other lipid A conjugates. These synthetic molecules have facilitated the elucidation of the structure-activity relationships of lipid A useful for the design and development of lipid A based therapeutics, such as those utilized to treat sepsis, and other medical applications, for example the use of monophosphoryl lipid A as a carrier molecule for the study of fully synthetic self-adjuvanting conjugate vaccines. These topics are also briefly covered in the current review.

• Authors: Jian Gao, Zhongwu Guo
• Journal: Medicinal research reviews (Med Res Rev) Vol. 38 Issue 2 Pg. 556-601 (03 2018) ISSN: 1098-1128 [Electronic] United States
• PMID: 28621828 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Lipid A
• Vaccines
• monophosphoryl lipid A

Topics

• Animals
• Biosynthetic Pathways
• Humans
• Lipid A (analogs & derivatives, biosynthesis, chemistry, pharmacology)
• Vaccines (immunology)