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Selective N-glycan editing on living cell surfaces to probe glycoconjugate function

Tang Feng, Zhou Mang, Qin Ken, Shi Wei, Yashinov Ansor, Yang Yang, Yang Liyun, Guan Dongliang, Zhao Lei, Tang Yubo, Chang Yujie, Zhao Lifen, Yang Huaiyu, Zhou Hu, Huang Ruimin, Huang Wei

Journal:Nature Chemical Biology

IF:12.59

DOI:10.1038/s41589-020-0551-8

PMID:32483376

Published:2020-06-01

research field:

Abstract

Cell surfaces are glycosylated in various ways with high heterogeneity, which usually leads to ambiguous conclusions about glycan-involved biological functions. Here, we describe a two-step chemoenzymatic approach for N -glycan-subtype-selective editing on the surface of living cells that consists of a first ‘delete’ step to remove heterogeneous N -glycoforms of a certain subclass and a second ‘insert’ step to assemble a well-defined N -glycan back onto the pretreated glyco-sites. Such glyco-edited cells, carrying more homogeneous oligosaccharide structures, could enable precise understanding of carbohydrate-mediated functions. In particular, N -glycan-subtype-selective remodeling and imaging with different monosaccharide motifs at the non-reducing end were successfully achieved. Using a combination of the expression system of the Lec4 CHO cell line and this two-step glycan-editing approach, opioid receptor delta 1 (OPRD1) was investigated to correlate its glycostructures with the biological functions of receptor dimerization, agonist-induced signaling and internalization.

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