Chemoenzymatic Probes for Detecting and Imaging Fucose-α(1-2)-galactose Glycan Biomarkers

Abstract

The disaccharide motif fucose-α(1-2)-galactose (Fucα(1-2)Gal) is involved in many important physiological processes, such as learning and memory, inflammation, asthma, and tumorigenesis. However, the size and structural complexity of Fucα(1-2)Gal-containing glycans have posed a significant challenge to their detection. We report a new chemoenzymatic strategy for the rapid, sensitive detection of Fucα(1-2)Gal glycans. We demonstrate that the approach is highly selective for the Fucα(1-2)Gal motif, detects a variety of complex glycans and glycoproteins, and can be used to profile the relative abundance of the motif on live cells, discriminating malignant from normal cells. This approach represents a new potential strategy for biomarker detection and expands the technologies available for understanding the roles of this important class of carbohydrates in physiology and disease.

Development of orally active inhibitors of protein and cellular fucosylation

“…A common approach has been through the utilization of novel monosaccharides that become incorporated or alter protein glycan structures. These include such molecules as 5-alkynylfucose (10,12), 5-thio-N-acetylglucosamine (13), 5-or 6-fluoro-galactofuranose (7), 3-fluoro-N-acetyl-neuraminic acid (11), azidosugars such as N-azidoacetylgalactosamine or N-azidoacetylglucosamine (1,14), 4-fluoro-glucosamine (15), 5-thiofucose (16), and 2-fluorofucose peracetate (11,17). Another method to modify protein glycans involves inhibition of enzymes that mediate glycosylation or glycan maturation with agents such as castanospermine (18), swainsonine (19), and the anti-type 1 Gaucher disease drug, N-butyldeoxynojirimycin (20).…”

CHoMP: A Chemoenzymatic Histology Method Using Clickable Probes

“…disaccharides or trisaccharides, since unnatural monosaccharide incorporation via biosynthetic pathways leads to incorporation of the unnatural substrate into many different polysaccharide glycoforms. [20] Because peripheral, higher-order glycans, rather than monosaccharides, encode information for cell-surface receptor recognition to trigger specific downstream signaling [21] ; there is an unmet need to develop methods for their detection.…”

Glycoprotein Disease Markers and Single Protein-omics

“…In conclusion, novel discovery strategies, including analysis of autoantibodies (77,98), arrays (42,99), glycopeptide enrichment coupled with mass spectrometric identification (39,43,100), innovations in cellular glycobiology (101,102), and chemoenzymatic methods (103)(104)(105) continue to expand the pipeline of glycoproteomic biomarker candidates. Detailed characterization of the relevant site-specific glycoforms and targeted quantification of protein glycoforms by innovative immunoassays and alternative methods, including mass spectrometric quantification, are expected to enhance current clinical diagnostic options.…”