Glycopeptides are peptides that contain carbohydrate moieties (glycans) covalently attached to the side chains of the amino acid residues that constitute the peptide.
Over the past few decades it has been recognised that glycans on cell surface (attached to membrane proteins or lipids) and those bound to proteins (glycoproteins) play a critical role in biology. For example, these constructs have been shown to play important roles in fertilization, the immune system, brain development, the endocrine system, and inflammation.
The synthesis of glycopeptides provides biological probes for researchers to elucidate glycan function in nature and products that have useful therapeutic and biotechnological applications.
Native chemical ligation (NCL) is a convergent synthetic strategy based on the linear coupling of glycopeptide fragments. This technique makes use of the chemoselective reaction between a N-terminal cysteine residue on one peptide fragment with a thio-ester on the C-terminus of the other peptide fragment as illustrated below. Several derivatives of vancomycin are currently being developed, including oritavancin and dalbavancin (both lipoglycopeptides). Possessing longer half-lives than vancomycin, these newer candidates may demonstrate improvements over vancomycin due to less frequent dosing and activity against vancomycin-resistant bacteria. Vancomycin is usually given intravenously, as an infusion, and can cause tissue necrosis and phlebitis at the injection site if given too rapidly. Pain at site of injection is indeed a common adverse event. One of the side-effects is red man syndrome, an idiosyncratic reaction to bolus caused by histamine release. Some other side-effects of vancomycin are nephrotoxicity including kidney failure and interstitial nephritis, blood disorders including neutropenia, and deafness, which is reversible once therapy has stopped. 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.
Oral preparations of vancomycin are available, however they are not absorbed from the lumen of the gut, so are of no use in treating systemic infections.