Enzymatic Building Block Synthesis for Automated Solid Phase Glycan Assembly

Automated chemical oligosaccharide synthesis is an attractive concept that has been successfully applied to a large number of target structures, but requires excess quantities of suitably protected and activated building blocks. Here we demonstrate the use of biocatalysis to supply such reagents for automated synthesis. By using the promiscuous NmLgtB‐B β1‐4 galactosyltransferase from Neisseria meningitidis we demonstrate fast and robust access to the LacNAc motif, common to many cell surface glycans starting from either lactose or sucrose as glycosyl donors. The enzymatic product was shown to be successfully incorporated, en bloc, into a tetrasaccharide target using automated assembly.