Glycopeptidomimetics: an underexplored tool in carbohydrate and peptide chemistry

Glycopeptidomimetics are structurally modified analogues of glycopeptides incorporating non-natural peptide-like scaffolds bearing native or modified glycan motifs. Glycopeptides, glycomimetics and peptidomimetics have each been extensively investigated across chemical biology and medicinal chemistry, however the intersection of these fields remains comparatively underexplored. This is surprising given the growing interest in carbohydrate-based recognition, targeting and therapeutic strategies, particularly in the context of cancer, infection and antimicrobial resistance. The replacement or modification of the native peptide component of glycopeptides offers glycopeptidomimetics opportunities to tune stability, conformation, multivalent presentation and biological activity, while retaining the molecular recognition features associated with carbohydrate structures. This review provides an overview of the synthesis and applications of glycopeptidomimetics reported to date, including glycopeptoids, glycodepsipeptides and other carbohydrate-containing peptidomimetic systems. Key successes, current limitations and emerging design principles are discussed, with particular emphasis on how this underdeveloped class of glycoconjugates may contribute to future advances in therapeutic discovery, diagnostics and chemical biology.