Oral Presentation 10th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2025

Synthesis of glycopeptides by rapid flow-based peptide synthesis (129107)

Yuta Maki 1 , Shintaro Yamaguchi 2 , Ryo Okamoto 1 , Kohtaro Hirao 1 , Bradley Pentelute 3 , Yasuhiro Kajihara 1
  1. Department of Chemistry and FRC, The University of Osaka, Toyonaka, OSAKA, Japan
  2. Department of Chemistry, The University of Osaka, Toyonaka, Osaka, Japan
  3. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States

Chemical synthesis of glycopeptides and glycoproteins has enabled us to investigate the functions of glycans at molecular level.ref1 However, preparation of glycoproteins requires several weeks to several months by current synthetic methods because of multiple syntheses of glycopeptides and repetitive ligation reactions.

In this work, we developed a rapid glycopeptide synthesis by flow-based solid-phase peptide synthesis (SPPS). First, we prepared Fmoc-Asn(acetylated oligosaccharide)-OH by isolation and chemical modifications, and then we used the building block for flow-based Fmoc-SPPS, which enables peptide elongation within 3 minutes.ref2 As a result, we synthesized a 25-mer peptide having the oligosaccharide within 2 hours. Additional hydrazine treatment yielded desired glycopeptide having a human-type oligosaccharide. Moreover, we also demonstrated synthesis of full-length glycoproteins (CD59 and CCL1) using automated fast-flow peptide synthesis (AFPS).ref3 In this presentation, we will present a detail of our efficient flow-based glycopeptide synthesis.

1. Maki, Y.; Okamoto, R.; Izumi, M.; Kajihara, Y. J. Am. Chem. Soc. 2020, 142, 20671.

2. (a) Simon, M. D.; Heider, P. L.; Adamo, A.; Vinogradov, A. A.; Mong, S. K.; Li, X.; Berger, T.; Policarpo, R. L.; Zhang, C.; Zou, Y.; Liao, X.; Spokoyny, A. M.; Jensen, K. F.; Pentelute, B. L. Chem. Bio. Chem. 2014, 15, 713. (b) Simon, M. D.; Maki, Y.; Vinogradov, A. A.; Zhang, C.; Yu, H.; Lin, Y.-S.; Kajihara, Y.; and Bradley L. Pentelute, B. L. J. Am. Chem. Soc. 2016, 138, 12099.

3. Hartrampf, N.; Saebi, A.; Poskus, M.; Gates, Z. P.; Callahan, A. J.; Cowfer, A. E.; Hanna, S.; Antilla, S.; Schissel, C. K.; Quartararo, A. J.; Ye, X.; Mijalis, A. J.; Simon, M. D.; Loas, A.; Liu, S.; Jessen, C.; Nielsen, T. E.; Pentelute, B. L. Science, 2020, 368, 980.