Developing a Library of Mannose-Based Mono- and Disaccharides: A General Chemoenzymatic Approach to Monohydroxylated Building Blocks

Lisa Tanzi,Teresa Recca,Teodora Bavaro,Sara Marzatico,Yongmin Zhang,Marco Terreni,Marina Simona Robescu

doi:10.3390/molecules25235764

Abstract

Regioselective deprotection of acetylated mannose-based mono- and disaccharides differently functionalized in anomeric position was achieved by enzymatic hydrolysis. Candida rugosa lipase (CRL) and Bacillus pumilus acetyl xylan esterase (AXE) were immobilized on octyl-Sepharose and glyoxyl-agarose, respectively. The regioselectivity of the biocatalysts was affected by the sugar structure and functionalization in anomeric position. Generally, CRL was able to catalyze regioselective deprotection of acetylated monosaccharides in C6 position. When acetylated disaccharides were used as substrates, AXE exhibited a marked preference for the C2, or C6 position when C2 was involved in the glycosidic bond. By selecting the best enzyme for each substrate in terms of activity and regioselectivity, we prepared a small library of differently monohydroxylated building blocks that could be used as intermediates for the synthesis of mannosylated glycoconjugate vaccines targeting mannose receptors of antigen presenting cells.

Highlights

Oligosaccharides are involved in the modulation of biomolecules properties and in the communication between cells; they play important roles in a variety of physiological and pathological processes, such as cell growth and proliferation, angiogenesis, protein folding and degradation, cell-cell communication, cell-pathogen interactions and immune response [1]
In the present work we report on a comparison between immobilized Candida rugosa lipase (CRL)
Considering that the acetylated monosaccharides and disaccharides are not completely soluble in buffer, we evaluated the stability of soluble acetyl xylan esterase from Bacillus pumilus (AXE) in

Summary

Introduction

Oligosaccharides are involved in the modulation of biomolecules properties and in the communication between cells; they play important roles in a variety of physiological and pathological processes, such as cell growth and proliferation, angiogenesis, protein folding and degradation, cell-cell communication, cell-pathogen interactions and immune response [1]. Oligosaccharides often occur as glycoconjugates attached to other macromolecules, such as lipids (glycolipids) and proteins (glycoproteins) [2]. Glycoconjugates can promote the immune response through the production of antibodies against a specific target; their use as vaccines has been proven to be a successful strategy to prevent infectious diseases [3]. Mannose-based glycoconjugates were investigated for improving antigens up-take mediated via the mannose receptor (MR) of human antigen presenting cells (APCs).

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Conclusion