Chemoselective Solution- and Solid-Phase Synthesis of Disulfide-Linked Glycopeptides

Area of Science:

• Biochemistry
• Organic Chemistry
• Glycobiology

Background:

• Glycosylation of peptides and proteins is crucial for mimicking post-translational modifications and enhancing peptide delivery.
• Sulfur-mediated glycosylation offers improved chemical and metabolic stability in glycoconjugates.

Purpose of the Study:

• To develop a simple and chemoselective method for preparing disulfide-linked glycopeptides.
• To demonstrate the utility of this method in both solution-phase and solid-phase peptide synthesis.

Main Methods:

• Utilizing acetate-protected glycosylsulfenyl hydrazines for reaction with cysteine thiol groups.
• Applying the method to both free peptides and during solid-phase peptide synthesis (SPPS).
• Demonstrating the efficiency with unprotected carbohydrates, eliminating deprotection steps.

Main Results:

• Successful and chemoselective formation of disulfide-linked glycopeptides.
• High yields achieved using the described glycosylation methodology.
• The procedure is effective with both protected and unprotected carbohydrates.

Conclusions:

• The reported method provides straightforward access to disulfide-linked glycopeptides.
• These glycopeptides have significant potential in structural glycobiology, pharmacology, and therapeutics.
• The methodology simplifies the synthesis of valuable glycoconjugates for diverse biological applications.