A new method for the synthesis of neoglycopeptides

A new method for conjugation of small carbohydrates to peptides based on maleimido-thiol chemistry is described. The reducing carbohydrate is reacted with S-trityl-2-mercaptoethylamine in methanol. The resulting Schiff base is then stabilized by acetylation with acetic anhydride to give an S-trityl-protected glycosylamide. Activation of the carbohydrate is effected by brief treatment with trifluoroacetic acid/triisopropylsilane, followed by precipitation in ether. The thiol-functionalized carbohydrate is then reacted with a maleimido-modified peptide to give a neoglycopeptide. The potential of this method was investigated using maltose as the model compound. Furthermore, we prepared five maleimido-modified model peptides. In contrast to some literature reports, we found that the maleimido group is stable to treatment trifluoroacetic acid/triisopropylsilane which was used to cleave the modified peptides from the resin.