Glycopeptide

A glycopeptide is a molecule that combines a peptide backbone with covalently attached carbohydrate (glycan) units. The glycan chains can vary in size and composition, influencing properties such as solubility, stability, and recognition by other biomolecules. Glycopeptides arise in biology both as natural products and as products of post-translational modification, where sugars are grafted onto peptide backbones during protein maturation.

Attachment sites and linkages vary: most commonly N-glycosylation on asparagine or O-glycosylation on serine or threonine. Glycan structures range from simple monosaccharides to complex branched oligosaccharides, yielding microheterogeneity. The type of linkage and sugar composition affect folding, receptor interactions, and pharmacokinetics in biological systems.

Glycopeptide antibiotics (GPAs) are a notable subclass produced by actinomycete bacteria. Examples include vancomycin, teicoplanin, dalbavancin, oritavancin, and telavancin. They inhibit bacterial cell-wall synthesis by binding the D-Ala–D-Ala terminus of peptidoglycan precursors, thereby blocking cross-linking. GPAs are primarily used against Gram-positive infections, especially methicillin-resistant Staphylococcus aureus, and are usually administered intravenously. Resistance can arise when bacteria alter the target to D-Ala–D-Lac, reducing drug binding.

Beyond antibiotics, glycopeptides also occur as glycosylated fragments of proteins and in analytical contexts, where glycopeptide profiling aids proteomics and the study of protein function. The field encompasses both natural products and post-translationally modified biomolecules with diverse biological roles.