Chemoselective solution- and solid-phase synthesis of disulfide-linked glycopeptides
Banisalman, Katreen A.F. Polykandritou, A. Morais, Goreti R. Falconer, Robert A.
Banisalman, Katreen A.F.
Polykandritou, A.
Morais, Goreti R.
Falconer, Robert A.
Publication Date
2022-10
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© 2022 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
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2022
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Abstract
Glycosylation of peptides and proteins is a widely employed strategy to mimic important post-translational modifications or to modulate the physicochemical properties of peptides to enhance their delivery. Furthermore, glycosylation via a sulfur atom imparts increased chemical and metabolic stability to the resulting glycoconjugates. Herein, we report a simple and chemoselective procedure to prepare disulfide-linked glycopeptides. Acetate-protected glycosylsulfenyl hydrazines are shown to be highly reactive with the thiol group of cysteine residues within peptides, both in solution and as part of conventional solid-phase peptide synthesis protocols. The efficiency of this glycosylation methodology with unprotected carbohydrates is also demonstrated, which avoids the need for deprotection steps and further extends its utility, with disulfide-linked glycopeptides produced in excellent yields. Given the importance of glycosylated peptides in structural glycobiology, pharmacology, and therapeutics, the methodology outlined provides easy access to disulfide-linked glycopeptides as molecules with multiple biological applications.
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Banisalman KA, Polykandritou A, Barnieh FM et al (2022) Chemoselective solution- and solid-phase synthesis of disulfide-linked glycopeptides. The Journal of Organic Chemistry. 87(21): 14026-14036.
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