Synthesis and binding affinity analysis of positional thiol analogs of mannopyranose for the elucidation of sulfur in different position

Abstract

Synthetic routes towards thio-α/β-d-mannose derivatives are presented. Double parallel or double serial inversion was successfully applied in the efficient synthesis of 2-thio- or 2,4-di-thio-mannoside derivatives. The protein recognition properties of the synthesized positional thiol analogs of mannose were then evaluated in a competition binding assay with the model lectin Concanavalin A (Con A), in order to investigate the roles of thiol group in the different position of the mannopyranose ring in binding affinity. Though the substitution of oxygen atom with sulfur atom in the methyl α-d-mannoside ring usually displayed low or no binding affinity towards Con A, it was a surprise finding that the methyl 2-thio-α-d-mannoside displayed four times higher inhibition than methyl α-d-mannoside, indicating the particular importance of 2-position for modification of α-d-mannoside. Methyl 3-thio-α-d-mannoside also displayed inhibition towards Con A, indicating that the O-atom at the C-3 position is less important in the binding site.