Rapid Chemo-Enzymatic Synthesis of Peracetylated GlcNAcβ3Galβ-Aglycones

Abstract

The inhibition of sialyl Lewis X can prevent unwanted cellular extravasation that is associated with inflammatory diseases and tumor metastasis. Described is an efficient methodology to prepare peracetylated GlcNAcβ3Gal-aglycone disaccharides subsequently used as metabolic decoys to inhibit sialyl Lewis X expression. Four glycosides were synthesized from one single parent disaccharide that in turn was prepared by large-scale enzymatic synthesis. The procedure avoids lengthy and inefficient synthetic steps to afford the desired disaccharides quickly with good overall yields.

Keywords:

• Disaccharides
• Decoy
• Sialyl Lewis X
• Glycosyltransferase

ACKNOWLEDGEMENTS

P.H.S. gratefully acknowledges financial support from NIH (5 R01 HL64799-06 and 5 P01 CA071932-10). J.D.E. gratefully acknowledges financial support from NIH (CA112278). We thank Dr. V. Mountain for critically editing this manuscript. We would like to thank Dr. Warren Wakarchuk and Dr James Paulson for the kind gift of lgtA β-3-N-acetylglucosaminyltransferase.

N. Merbouh and J. R. Brown contributed equally to the work and should be considered as first coauthors.