Clickable Galactose Analogues for Imaging Glycans in Developing Zebrafish

Area of Science:

• Biochemistry
• Glycobiology
• Developmental Biology

Background:

• Galactose is a key monosaccharide for complex glycan synthesis in vertebrates.
• Metabolic defects in galactose lead to diseases like galactosemia and lysosomal storage disorders.
• Visualizing metabolic flux is crucial for understanding these diseases.

Purpose of the Study:

• To develop novel bioorthogonal metabolic reporters for galactose.
• To overcome the intolerance of the galactose salvage pathway to unnatural analogues.
• To visualize *in vivo* glycosylation dynamics using modified UDP-Gal probes.

Main Methods:

• Synthesized and tested unnatural galactose and galactose-1-phosphate analogues.
• Modified uridine diphosphate galactose (UDP-Gal) to create effective metabolic probes.
• Utilized 6-alkynyl UDP-Gal and click chemistry for *in vivo* glycan labeling in zebrafish.

Main Results:

• The galactose salvage pathway showed intolerance to tested galactose and galactose-1-phosphate analogues.
• Modified UDP-Gal analogues proved effective for *in vivo* glycan labeling.
• Visualized glycosylation during zebrafish development, identifying accumulation in specific structures.

Conclusions:

• UDP-Gal analogues represent a new class of glycan metabolic probes.
• These probes enable visualization of physiological and pathological glycosylation changes *in vivo*.
• This approach aids in understanding diseases related to galactose metabolism.