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Updated: Sep 18, 2025

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
Published on: October 4, 2017
Cycloadditions as a Sweet Route to 'Double C-Glycosylation'
Kevin P P Mahoney1,2,3, Rosemary Lynch1, Rhea T Bown1
1School of Chemistry, Integrated Institute of Engineering, and BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK.
None:
Pharmaceuticals, such as the antibiotic erythromycin, and sodium-dependent glucose transporter (SGLT1 & SGTL2) inhibitors such as Bexagliflozin (diabetes) and Sotagliflozin (heart disease), are often sugar-decorated (glycosylated). Glycosylation is a key component of the binding motif in SGLT inhibitors and, in natural products, glycosylation often confers improved bioactivity and bioavailability. Whilst a single C-glycoside link between a sugar moiety and its aglycone core is a common feature in natural products isolated to date, only a small number, including the antibiotics granaticin and sarubicin, are covalently bonded twice to a single sugar moiety. The way in which this "double C-glycosylation" is naturally mediated is not yet known, yet has been speculated on. Here, we report the exploration and development of a potentially biomimetic procedure that utilises intermolecular cycloaddition chemistry to access new "double C-glycosylated" products and enables the creation of bridged polycyclic ethers from a common maltol-derived oxidopyrylium salt precursor.
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