Synthesis of Biologically Active N- and O-Linked Glycans with Multisialylated Poly-N-acetyllactosamine Extensions Using P. damsela 伪2-6 Sialyltransferase

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• 作者：Corwin M. Nycholat ; Wenjie Peng ; Ryan McBride ; Aristotelis Antonopoulos ; Robert P. de Vries ; Zinaida Polonskaya ; M.G. Finn ; Anne Dell ; Stuart M. Haslam ; James C. Paulson
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：December 11, 2013
• 年：2013
• 卷：135
• 期：49
• 页码：18280-18283
• 全文大小：437K
• 年卷期：v.135,no.49(December 11, 2013)
• ISSN：1520-5126

文摘

Sialosides on N- and O-linked glycoproteins play a fundamental role in many biological processes, and synthetic glycan probes have proven to be valuable tools for elucidating these functions. Though sialic acids are typically found 伪2-3- or 伪2-6-linked to a terminal nonreducing 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 Neu5Ac伪2-6Gal epitopes. Here, we have developed an efficient approach for the synthesis of a library of N- and O-linked glycans with multisialylated poly-LacNAc extensions, including naturally occurring multisialylated core-3 O-linked glycans. We have found that a recombinant 伪2-6 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 Neu5Ac伪2-6Gal 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. Polyclonal IgY antibodies specific for internal sialoside epitopes were elicited in inoculated chickens.