Dual-sugar imaging using isonitrile and azido-based click chemistries.

Area of Science:

• Glycobiology
• Chemical Biology
• Cancer Research

Background:

• Aberrant glycosylation is a hallmark of cancer.
• Targeting specific glycans is crucial for cancer diagnostics and therapeutics.
• Current methods for visualizing multiple glycans simultaneously are limited.

Purpose of the Study:

• To develop a novel metabolic labeling strategy for simultaneous visualization of distinct cancer cell glycoproteins.
• To establish a versatile chemical biology approach for glycan imaging.

Main Methods:

• Metabolic labeling of N-acetylglucosamine (GlcNAc) in conjunction with either N-acetylgalactosamine (GalNAc) or N-acetylmannosamine (ManNAc).
• Utilized a combination of isonitrile- and azide-based click chemistries.
• Employed specifically designed fluorescent probe molecules reactive towards azido or isonitrile groups.

Main Results:

• Successfully achieved metabolic labeling of distinct sugar moieties within cancer cells.
• Demonstrated co-visualization of cancer cell glycoproteins using orthogonal chemical probes.
• Validated the specificity and efficiency of the developed labeling and imaging approach.

Conclusions:

• This work presents the first report of metabolically labeling GlcNAc with either GalNAc or ManNAc.
• The developed method enables simultaneous imaging of multiple cancer-associated glycoproteins.
• This approach holds significant potential for advancing cancer biomarker discovery and understanding glycosylation changes in disease.