Efficient Preparation and Bioactivity Evaluation of Glycan-Defined Glycoproteins

Ji Young Hyun, Sanggil Kim, Chang Hee Lee, Hyun Soo Lee, Injae Shin

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2 Citations (Scopus)


Owing to the generation of heterogeneous glycoproteins in cells, it is highly difficult to study glycoprotein-mediated biological events and to develop biomedical agents. Thus, general and efficient methods to prepare homogeneous glycoproteins are in high demand. Herein, we report a general method for the efficient preparation of homogeneous glycoproteins that utilizes a combination of genetic code expansion and chemoselective ligation techniques. In the protocol to produce glycan-defined glycoproteins, an alkyne tag-containing protein, generated by genetic encoding of an alkynylated unnatural amino acid, was quantitatively coupled via click chemistry to versatile azide-appended glycans. The glycoproteins produced by the present strategy were found to recognize mammalian cell-surface lectins and enter the cells through lectin-mediated internalization. Also, cell studies exhibited that the glycoprotein containing multiple mannose-6-phosphate residues enters diseased cells lacking specific lysosomal glycosidases by binding to the cell-surface M6P receptor, and subsequently migrates to lysosomes for efficient degradation of stored glycosphingolipids.

Original languageEnglish
Pages (from-to)1930-1940
Number of pages11
JournalACS Chemical Biology
Issue number10
Publication statusPublished - 2021 Oct 15

Bibliographical note

Funding Information:
This work was supported financially by the National Research Foundation of Korea (NRF; grant no. 2020R1A2C3003462 to I.S. and NRF-2019R1A2C1010665 to H.L.) and the Korea Research Institute of Chemical Technology (KRICT; grant no. SI2031-40 to J. Y. H.).

Publisher Copyright:
© 2021 American Chemical Society.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine


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