Open AccessChemoselective Solution- and Solid-Phase Synthesis of Disulfide-Linked Glycopeptides
Author(s) -
Katreen A. F. Banisalman,
Athina Polykandritou,
Francis M. Barnieh,
Goreti Ribeiro Morais,
Robert A. Falconer
Publication year - 2022
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.2c01651
Subject(s) - glycopeptide , glycosylation , chemistry , combinatorial chemistry , glycoconjugate , disulfide bond , peptide , cysteine , glycan , biochemistry , bioconjugation , peptide synthesis , solid phase synthesis , glycoprotein , enzyme , antibiotics
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.