Glycopeptide antibiotics are a class of drugs of microbial origin that are composed of glycosylated cyclic or polycyclic nonribosomal peptides.

The extra lipophilicity not only enhances Lipid II binding but also creates a second mechanism of action whereby the antibiotic dissolves into the membrane and makes it more permeable.

[1] Corbomycin and complestatin are structurally and ancestrally related to vancomycin, but they work by inhibiting autolysins through binding to peptidoglycan, therefore preventing cell division,[2] neither is an approved drug.

It not only binds to Lipid II but also attacks MurG and transglycosylases (glycosyltransferases) which polymerize amino acid/sugar building blocks into peptidoglycan.

[4] Due to their toxicity, the use of first-generation glycopeptide antibiotics is restricted to patients who are critically ill, who have a demonstrated hypersensitivity to the β-lactams, or who are infected with β-lactam-resistant species, as in the case of methicillin-resistant Staphylococcus aureus.

The second-generation glycopeptides, or "lipoglycopeptides", have better binding to Lipid II due to the lipophilic moieties, expanding the antibacterial spectrum.

Over 90% of the dose is excreted in the urine, therefore there is a risk of accumulation in patients with renal impairment, so therapeutic drug monitoring (TDM) is recommended.