Integrated Chemoenzymatic Approach to Streamline the Assembly of Complex Glycopeptides in the Liquid Phase.

Wenjing Ma, Yaqi Deng, Zhuojia Xu, Xingbang Liu, Digantkumar G Chapla, Kelley W Moremen, Liuqing Wen, Tiehai Li

Journal of the American Chemical Society 2022 May 25

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Glycosylation of proteins is a complicated post-translational modification. Despite the significant progress in glycoproteomics, accurate functions of glycoproteins are still ambiguous owing to the difficulty in obtaining homogeneous glycopeptides or glycoproteins. Here, we describe a streamlined chemoenzymatic method to prepare complex glycopeptides by integrating hydrophobic tag-supported chemical synthesis and enzymatic glycosylations. The hydrophobic tag is utilized to facilitate peptide chain elongation in the liquid phase and expeditious product separation. After removal of the tag, a series of glycans are installed on the peptides via efficient glycosyltransferase-catalyzed reactions. The general applicability and robustness of this approach are exemplified by efficient preparation of 16 well-defined SARS-CoV-2 O-glycopeptides, 4 complex MUC1 glycopeptides, and a 31-mer glycosylated glucagon-like peptide-1. Our developed approach will open up a new range of easy access to various complex glycopeptides of biological importance.

Citation

Wenjing Ma, Yaqi Deng, Zhuojia Xu, Xingbang Liu, Digantkumar G Chapla, Kelley W Moremen, Liuqing Wen, Tiehai Li. Integrated Chemoenzymatic Approach to Streamline the Assembly of Complex Glycopeptides in the Liquid Phase. Journal of the American Chemical Society. 2022 May 25;144(20):9057-9065