Design, synthesis and molecular docking study of α-triazolylsialosides as non-hydrolyzable and potent CD22 ligands

Ligand 1 was the first reported example of monomeric high-affinity synthetic CD22 ligand that regulated B cell activation in vitro, augmented antibody production and regulated immune responses in mice. Replacing O-glycoside linkage of 1 by nitrogen of triazole by click reaction afforded compounds which are as potent as the parent compound. The synthesis of the new compounds is straightforward with fewer synthetic steps and higher yield. Such a strategy provided stable ligand that can bind avidly and can be conjugated to drugs for B-cell targeting or multimeric formation. The new compounds were screened for their affinity to CD22, using surface plasmon resonance (SPR). Compound 12 was obtained as a bioisosteric analogue and an anomerically stable imitation of 1. It was, also, screened for MAG to test for selectivity and analyzed by molecular docking and dynamic simulation to explore the potential binding modes and source of selectivity within CD22. Our results could enable the development of small molecule drug capable of modulating the activity of CD22 in autoimmune diseases and malignancies derived from B-cells. (C) 2020 Elsevier Masson SAS. All rights reserved.