Abstract
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. Herein 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 as a complete unit into a tetrasaccharide target by automated assembly.
Highlights
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
The building block application has been provided by Broder et al.,[28] with an more specific investigation of different protective groups. In this case the advantages of the enzymatic synthesis we propose compared to this approach are the same as the above mentioned
We explore the towards the formation of the desired compound 2, we promiscuity of carbohydrate active enzymes that tolerate investigated a one pot three enzyme reaction using sucrose as protecting and activating groups which are needed for the starting material.[32]
Summary
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. Compared to the more common motifs bearing a central GlcNAcb1-3Gal sequence the b1-4 linkage is synthetically more challenging, because of the reduced reactivity of the axial hydroxyl group.[21] In addition, whilst Type 1 (b1-3) and 2 (b1-4) polyLacNAc sequence can be generated enzymatically,[22,23] the required enzyme with b1-4 linkage selectivity is currently not available and this linkage has to be generated chemically.
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