N- and O-linked glycans are biologically important post-translational modifications of glycoproteins on the cell surface, which play a fundamental role in many processes, including cell adhesion, signal transduction, and immune response. Extended poly-N-acetyllactosamine ( pLN ) glycans found on glycoproteins as well as glycolipids of some cells, are able to be further modified by sialylation, fucosylation and O-sulfation. Extended sialosides have shown to influence receptor-binding specificity in different biological studies. Though sialic acids are typically found a2-3 or a2-6-linked to a terminal non-reducing end galactose, poly-LacNAc extended core-3 O-linked glycans isolated from rat salivary glands and human colonic mucins have been reported to contain multiple internal Neu5Aca2-6Gal epitopes. Due to the complexity of natural glycans, the availability of synthetic structures for biological studies has been limiting. Here, we have developed an efficient approach for the synthesis of a library of N- and O-linked glycans with multi-sialylated poly-LacNAc extensions, including naturally occurring multi-sialylated core-3 O-linked glycans. We have found that a recombinant a2-6 sialyltransferase from Photobacterium damsela (Pd2,6ST) exhibits unique regioselectivity and is able to sialylate internal galactose residues in poly-LacNAc extended glycans which was confirmed by MS/MS analysis. Using a glycan microarray displaying this library we found that Neu5Aca2-6Gal specific influenza virus hemagglutinins, siglecs and plant lectins are largely unaffected by adjacent internal sialylation, and in several cases the internal sialic acids are recognized as ligands. (Funded by NIH Grant AI099274).

Synthesis of biologically active N- and O-linked glycans with multi-sialylated poly-N-acetyllactosamine extensions using P. damsela a2-6 sialyltransferase

247th National Meeting (2014)

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