Cell surfaces are glycosylated in various ways with high heterogeneity, which usually leads to ambiguous conclusions about glycan-involved biological functions.
A research team led by Prof. HUANG Wei at Shanghai Institute of Materia Medica of Chinese Academy of Sciences described 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.
This work was published in Nature Chemical Biology on June 1. Prof. HUANG Wei is the corresponding author, who is also a doctoral supervisor at University of Chinese Academy of Sciences. This work was supported by the National Natural Science Foundation of China, the National Science & Technology Major Project ‘Key New Drug Creation and Manufacturing Program’ of China, and the China Postdoctoral Science Foundation.
