Cut-insert-stitch editing reaction (CIStER) sequence for surgical chemical glycan editing

Area of Science:

• Carbohydrate Chemistry
• Synthetic Organic Chemistry
• Glycobiology

Background:

• Post-synthetic modification allows for the creation of diverse molecules from a single precursor.
• Synthetically inserting foreign glycans into existing carbohydrate structures remains a significant challenge in chemistry.

Purpose of the Study:

• To develop a novel, efficient chemical strategy for editing glycoconjugates.
• To demonstrate the versatility of the new method in synthesizing complex carbohydrate structures and glycohybrids.

Main Methods:

• A one-pot, three-step chemical approach termed 'cut-insert stitch-editing' (CIStER) was developed.
• The method involves cleaving an interglycosidic bond, intercepting the intermediate, activating a donor, and stitching to form new linkages.
• The reaction was validated by inserting arabinans and synthesizing glycohybrids with hydroxyacids.

Main Results:

• The CIStER reaction successfully inserted branched and linear arabinans, mimicking the Mycobacterium tuberculosis cell wall.
• The approach was extended to create glycohybrids by glycosylating serinyl, steroidal, and lipid hydroxyacids.

Conclusions:

• The developed CIStER reaction provides a powerful tool for the post-synthetic editing of glycoconjugates.
• This method enables the synthesis of complex oligosaccharides and glycohybrids with potential applications in various fields.