Chemoenzymatic synthesis of human natural killer-1-containing glycans and application as serum antibodies probes
Nature Synthesis(2023)
摘要
Despite the versatility of enzyme-mediated oligosaccharide assembly, it has as a limitation that not all glycosyl transferases or glycan-modifying enzymes are readily available to install all natural occurring terminal epitopes. Here a chemoenzymatic strategy is described in which a core oligosaccharide is assembled enzymatically that is subjected to chemical manipulations to install complex terminal epitopes. It provided an unprecedented panel of human natural killer-1 (HSO3–3GlcAβ1–3Galβ1–4GlcNAc)-containing oligosaccharides and derivatives thereof. The compounds were printed as a microarray to examine binding specificities of serum antibodies of patients suffering from anti-myelin-associated glycoprotein neuropathy. All samples required glucuronic acid for antibody binding; however, variable dependence was observed for the length of the LacNAc chain and sulfation of glucuronic acid. Most serum samples required a lacto-neohexaose backbone indicating glycosphingolipids are being targeted. The clinical spectrum of immunoglobulin M monoclonal gammopathy varies, and the glycan microarray provides a more reliable platform for disease diagnosis and prognosis. While enzyme-mediated oligosaccharide synthesis is versatile, it is often limited by the availability of glycosyl transferases. Now a chemoenzymatic strategy is reported, comprising enzymatic assembly of a core oligosaccharide followed by chemical manipulations, to produce a library of glycans that reveal binding specificities of serum antibodies.
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关键词
Carbohydrate chemistry,Carbohydrates,Glycobiology,Immunological disorders,Chemistry/Food Science,general
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