Semi-synthesis of Homogeneous Glycoproteins  — ASN Events
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  2. Peptide Chemistry II
  3. Semi-synthesis of Homogeneous Glycoproteins 

Semi-synthesis of Homogeneous Glycoproteins  (#53)

Yasuhiro Kajihara 1
  1. Department of Chemistry, Osaka University, Machikaneyama, Toyonaka, Japan

Oligosaccharides of protein surface play important roles in many biological events. In order to evaluate the function of oligosaccharides dependent on glycosylation positions and glycosylation number, we need efficient synthetic methods of glycoproteins having homogeneous oligosaccharides.1

In order to prepare homogeneous glycoproteins, we have studied the efficient semisynthetic method of peptide-thioester. Using long peptides prepared in E. Coli, we have studied the thioesterification of the peptide by the activation of a cysteine residue intentionally incorporated at the C-terminal.2-3  Thus we found that three types of thioesterification methods and these methods efficiently gave peptide-thioesters in moderate yield.  

In terms of coupling reaction of glycosyl-amino acid and peptide-thioester, we developed amino thioacid method.4 The coupling of a peptide-thioester with a glycosyl-amino thioacid efficiently yielded a peptide having glycosyl-amino thioacid at the C-terminal. Toward this glycopeptide-thioacid, ligation5 with a peptide having a cysteine at the N-terminal was performed in order to synthesize a target glycoprotein. 

In this presentation, I would discuss a new semi-synthetic method of glycoproteins.

  1. Murakami, M.; Kiuchi, T.; Nishihara, M.; Tezuka, K.; Okamoto, R.; Izumi, M.; Kajihara, Y., Chemical synthesis of erythropoietin glycoforms for insights into the relationship between glycosylation pattern and bioactivity. Science Advances 2016, 2, e1500678.
  2. Cowper, B.; Shariff, L.; Chen, W.; Gibson, S. M.; Di, W.-L.; Macmillan, D., Expanding the scope of N-S acyl transfer in native peptide sequences. Org. Biomol. Chem. 2015, 13 (27), 7469-7476.
  3. Kajihara, Y.; Kanemitsu, Y.; Nishihara, M.; Okamoto, R.; Izumi, M., Efficient synthesis of polypeptide-α-thioester by the method combining polypeptide expression and chemical activation for the semi-synthesis of interferon-γ having oligosaccharides. J. Pept. Sci. 2014, 20 (12), 958-963.
  4. Okamoto, R.; Haraguchi, T.; Nomura, K.; Maki, Y.; Izumi, M.; Kajihara, Y., Regioselective α-Peptide Bond Formation Through the Oxidation of Amino Thioacids. Biochemistry 2019, 58 (12), 1672-1678.
  5. Zhang, X.; Li, F.; Liu, C.-F., Synthesis of histone H3 proteins by a thioacid capture ligation strategy. Chem Commun 2011, 47 (6), 1746-1748.