Chemoenzymatic approaches to the imaging and detection of cancer relevant fucosylated glycoconjugates

Abstract

A major focus in the field of glycomics has been the development of new strategies for the detection and quantification of glycans and glycoconjugates. With alterations in glycoconjugate structure being a hallmark of various cancers, these strategies can discover new cancer biomarkers and be developed into new clin. diagnostic tools. Here we report chemoenzymic strategies for the rapid, sensitive detection of cancer-relevant fucosylated glycoconjugates. Our methods exploit non-mammalian glycosyltransferases that accept non-natural donor substrates. We then use "Click" chem. to append reporter tags for the detection of these glycans. We have developed methods for the detection of glycans contg. fucoseα(1-2)galactose (Fucα(1-2) Gal), a motif implicated cancer pathogenesis, as well as core fucosylated glycans, a carbohydrate modification that is upregulated in various cancer states and mediates cell signaling events. We demonstrate the specificity and utility of these methods for the detection of cancerous compared to healthy cells and tissues.