A new method for conjugation of carbohydrates to proteins using an aminooxy-thiol heterobifunctional linker.

A new, efficient, and mild protocol is presented for the coupling of saccharides to proteins. First, a heterobifunctional aminooxy-thiol linker is coupled to the bromoacylated protein to introduce aminooxy groups through thioether linkages. Condensation of the aminooxylated protein and aldehydo/keto-derivatized carbohydrates affords covalent saccharide-protein constructs. Uncoupled saccharide can be recovered in its original form. The scope of our protocol is exemplified by the coupling of neutral mono- and tetrasaccharides and a negatively charged ribitol-phosphate construct to BSA.