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 .