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Published on: October 4, 2017
Bis-S-Glycosylation of Disulfides
Shiyang Xu1, Fei Hu1, Shuoyingjie Wang1
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Angewandte Chemie (International Ed. in English)
|July 24, 2026
Summary
Researchers developed a new method for attaching multiple carbohydrate units to molecules, crucial for drug development. This technique enables the synthesis of targeted therapies and diagnostic tools by creating novel glycopeptides and conjugates.
Area of Science:
- Carbohydrate chemistry
- Glycobiology
- Medicinal chemistry
Background:
- Carbohydrates are vital in biological processes and drug discovery.
- Multivalent carbohydrate presentation enhances target binding (glycoside cluster effect).
- Existing methods struggle to attach multiple carbohydrate units efficiently.
Purpose of the Study:
- To develop a mild and efficient method for direct bis-S-glycosylation.
- To synthesize fully unprotected S-linked glycopeptides.
- To create novel glycosylated molecules for therapeutic and diagnostic applications.
Main Methods:
- Direct, stereoselective bis-S-glycosylation of dialkyl disulfide bonds in aqueous solution.
- Utilized glycosyl sulfinates as donors and tert-butyl hydroperoxide (tBuOOH) as oxidant.
- Employed a radical pathway to form cysteine-glycosyl linkages.
Main Results:
- Successfully installed two unprotected glycosyl units onto disulfide bonds.
- Synthesized fully unprotected S-linked glycopeptides.
- Demonstrated application in creating liver-targeting peptides and affibody-radionuclide conjugates.
Conclusions:
- The developed protocol offers a simple and robust strategy for synthesizing complex glycopeptides.
- This method facilitates the creation of advanced glycosylated biomolecules for targeted therapies.
- The findings advance carbohydrate chemistry and its application in drug development.
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