Synthesis and biological evaluation of mirror isomers of β-(1 → 3)-glucans as immune modulators

Abstract

β-(1 → 3)-glucan is widely distributed in the cell walls of bacteria, fungi, yeasts and algae. A variety of pharmacological effects of β-(1 → 3)-glucan have been demonstrated, including immune modulation. The enzyme recognition pocket can recognize the chirality of the ligand and often give rise to disparate biological activities. The bioactivity of the mirror-image isomers of natural oligosaccharides is scarcely studied due to the difficulty of acquiring them. In this study, we have successfully completed the total synthesis of the naturally occurring β-ᴅ-(1 → 3)-glucans and their mirror image β-ʟ-(1 → 3)-glucans containing three, four, eight, and twelve monosaccharides for the first time. Subsequently, the immunomodulatory activities of ᴅ- and ʟ-type β-glucans were evaluated to explore their bioactivity and preliminary mechanism of action. The results indicated that mirror-image β-(1 → 3)-glucans exerted bidirectional regulatory effects on M0/M1-type macrophages. The ᴅ-type β-(1 → 3)-glucans have the potential to regulate macrophage polarization through the GPCR and CR3 signalling pathways. In contrast, the ʟ-type β-(1 → 3)-glucans achieved bidirectional regulation of macrophage polarization by influencing cellular metabolism. The findings presented herein provide new evidence for the further investigation of the biological activities of oligosaccharides and their mirror image isomers.