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

• Published in: Glycoconjugate journal Vol. 40; no. 2; pp. 225 - 246
• Main Authors: Suganuma, Yuki, Imamura, Akihiro, Ando, Hiromune, Kiso, Makoto, Takematsu, Hiromu, Tsubata, Takeshi, Ishida, Hideharu
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2023; Springer Nature B.V
• Subjects: Acids; Aglycones; Alcohol; Animals; B-Lymphocytes - metabolism; Biochemistry; Biomedical and Life Sciences; CD22 antigen; Immunoglobulins; Lectins; Life Sciences; Ligands; Lymphocytes B; Mice; Pathology; Research Article; Sialic Acid Binding Ig-like Lectin 2 - metabolism; Signal Transduction; Sialoside; Sialic acid; Inhibitor; Chemical synthesis; CD22
• ISSN: 0282-0080; 1573-4986; 1573-4986
• DOI: 10.1007/s10719-023-10098-8

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.