Synthesis and Functional Study of Bacterial Glycoconjugates Triggering the Innate Immune System of Higher Animals

Abstract

Typical bacterial glycoconjugates, lipopolysaccharide (LPS) and peptidoglycan (PGN), which ubiquitously occur in a wide range of bacterial cells as important components of their cell envelope, have long been known to enhance the immunological responses of higher animals. Synthetic works and related biological investigations on LPS are reviewed which were performed to understand the molecular basis of this phenomena mainly by the author's and collaborating groups. Structural study followed by chemical synthesis of glycolipid part of LPS, named lipid A, proved it to exhibit all the biological activity described for LPS. Synthetic homogeneous lipid A and its derivatives were utilized for precise studies of their biological functions and interaction with receptor proteins. Similar research on PGN led to conclude its minimum active structure as muramyl dipeptide. Chemical synthesis gave unequivocal evidences for the concept that definite small molecular parts of LPS and PGN are recognized by its specific receptors and trigger our defense system which is now recognized as innate immunity.

Glycosyl Sulfonium Ions as Storable Intermediates for Glycosylations

“…The yield of 15 was moderate, however, presumably because of low reactivity of glycosyl acceptor 10 due to the steric hindrance of the N -Phth group. , The resulting thioglycosides 14 and 15 could be directly used as glycosyl donors for the subsequent glycosylations. The disaccharide 14 is a part of lipid A and disaccharide 15 is also a part of the core unit of N- linked oligosaccharide and Nod factor. , …”

Natural glycans and glycoconjugates as immunomodulating agents

“…Finally, lipopolysaccharides (LPSs) of Gram-negative bacteria are recognized by the innate immune system, and therefore are responsible for the induction of the production of many kinds of mediators, such as cytokines and NO. 145 LPSs have been known as the most potent immunostimulant from microorganisms; in particular, lipid A, the glycolipid component (Fig. 16), has been demonstrated to be the chemical responsible for its endotoxic activity.…”