Synthesis of structurally-defined polymeric glycosylated phosphoprenols as potential lipopolysaccharide biosynthetic probes. Issue 36 (19th August 2021)

• Record Type: Journal Article
• Authors: Wang, Lei; Lowary, Todd L.
• Is Part Of: Chemical science. Volume 12:Issue 36(2021)
• Page Start: 12192
• Page End: 12200
• Publication Date: 2021-08-19
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1sc03852d
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : The synthesis of lipid-linked polysaccharides containing 11 and 27 monosaccharides via a 'frame-shift' strategy is described. The work provides biosynthetic probes and highlights challenges in synthesizing structurally-defined polymeric glycans. Abstract : The biosynthesis of lipopolysaccharide (LPS), a key immunomodulatory molecule produced by gram-negative bacteria, has been a topic of long-term interest. To date, the chemical probes used as tools to study LPS biosynthetic pathways have consisted primarily of small fragments of the larger structure ( e.g., the O-chain repeating unit). While such compounds have helped to provide significant insight into many aspects of LPS assembly, understanding other aspects will require larger, more complex probes. For example, the molecular interactions between polymeric LPS biosynthetic intermediates and the proteins that transfer them across the inner and outer membrane remain largely unknown. We describe the synthesis of two lipid-linked polysaccharides, containing 11 and 27 monosaccharide residues, that are related to LPS O-chain biosynthesis in Escherichia coli O9a. This work has led not only to multi-milligram quantities of two biosynthetic probes, but also provided insights into challenges that must be overcome in the chemical synthesis of structurally-defined polysaccharides.