Abstract

Mammalian cell membranes are decorated by the glycocalyx, which offer versatile means of generating biochemical signals. By manipulating the set of glycans displayed on cell surface, it is vital for gaining insight into the cellular behavior modulation and medical and biotechnological adhibition. Although genetic engineering is proven to be an effective approach for cell surface modification, the technique is only suitable for natural and genetically encoded molecules. To circumvent these limitations, non-genetic approaches are developed for modifying cell surfaces with unnatural but functional groups. Here, we review latest development of metabolic glycoengineering (MGE), which enriches the chemical functions of the cell surface and is becoming an intriguing new tool for regenerative medicine and tissue engineering. Particular emphasis of this review is placed on discussing current applications and perspectives of MGE.

Highlights

  • The cell surfaces are dominated by multiple functional molecules, which play essential roles in regulating intercellular communications, molecules selective transportation and intracellular associated signaling pathways (Abbina et al, 2018)

  • Compared with other molecules on cell surface, glycans signify the function of a cell and specify how it interacts with its surroundings (Du and Yarema, 2010)

  • There are abundant chemical groups on the cell surface, only a handful of functional groups can be used for direct covalent bond formation reactions under suitable conditions

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Summary

INTRODUCTION

The cell surfaces are dominated by multiple functional molecules, which play essential roles in regulating intercellular communications, molecules selective transportation and intracellular associated signaling pathways (Abbina et al, 2018). Previous reports have shown that using surface-displayed genetically engineered chimeric antigen receptor (CAR) T cells to recognize cancer antigens for the treatment of acute lymphoblastic leukemia (Kuehn, 2017). Nagasundaram et al(Nagasundaram et al, 2020) found a marked reduction in adhesion of MCF7 breast cancer cells to laminin upon treatment with different ManNAc analogs They found that application of all non-natural sialic acid precursors downregulated N-acetylneuraminic acid (Neu5Ac) and polysialic acids (polySia), and further suppressed adhesion and migration. ManNProp reportedly promoted monocytic differentiation of HL60-cells (Horstkorte et al, 2004) Both Ac5ManNTProp and Ac5ManNTBut, which display thiol groups on the cell surface, were found to suppress adipogenic differentiation in hADSCs, but they did not interfere with differentiation to a glial lineage (Du et al, 2021).

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