2. Academic Validation
  3. Improved synthesis of CD22-binding sialosides and its application for further development of potent CD22 inhibitors

Improved synthesis of CD22-binding sialosides and its application for further development of potent CD22 inhibitors

  • Glycoconj J. 2023 Apr;40(2):225-246. doi: 10.1007/s10719-023-10098-8.
Yuki Suganuma 1,  Akihiro Imamura 2 3,  Hiromune Ando 4,  Makoto Kiso 1,  Hiromu Takematsu 5,  Takeshi Tsubata 6,  Hideharu Ishida 7 8
Affiliations

Affiliations

  • 1 Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
  • 2 Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan. [email protected].
  • 3 Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan. [email protected].
  • 4 Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
  • 5 Faculty of Medical Technology, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
  • 6 Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
  • 7 Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan. [email protected].
  • 8 Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan. [email protected].
PMID: 36708410 DOI: 10.1007/s10719-023-10098-8
Abstract

CD22, one of the sialic acid-binding immunoglobulin-like lectins (Siglecs), regulates B lymphocyte signaling via its interaction with glycan ligands bearing the sequence Neu5Ac/Gcα(2→6)Gal. We have developed the synthetic sialoside GSC-718 as a ligand mimic for CD22 and identified it as a potent CD22 Inhibitor. Although the synthesis of CD22-binding sialosides including GSC-718 has been reported by our group, the synthetic route was unfortunately not suitable for large-scale synthesis. In this study, we developed an improved scalable synthetic procedure for sialosides which utilized 1,5-lactam formation as a key step. The improved procedure yielded sialosides incorporating a series of aglycones at the C2 position. Several derivatives with substituted benzyl residues as aglycones were found to bind to mouse CD22 with affinity comparable to that of GSC-718. The new procedure developed in this study affords sialosides in sufficient quantities for cell-based assays, and will facilitate the search for promising CD22 inhibitors that have therapeutic potential.

Keywords

CD22; Chemical synthesis; Inhibitor; Sialic acid; Sialoside.

Figures
Products