Semisynthetic glycopeptides: chemistry, structure-activity relationships and prospects

Glycopeptides are a class of naturally occurring antibiotics produced by fermentation of microorganisms. They inhibit cell wall biosynthesis in bacteria by forming a complex with the C-terminal D-alanyl-D-alanine of growing peptidoglycan chains. Glycopeptides are active against Gram-positive bacteria including the major pathogens. Among all the glycopeptides that have been discovered, only vancomycin and teicoplanin are on the market for the clinical use. By modification of the natural glycopeptide it is possible to increase its activity against methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci. Basic amides of teicoplanin aglycon have produced one compound endowed with interesting activity against Gram-negative bacteria because of its ability to cross the outer membrane of this last bacteria. Selective degradation of teicoplanin has given a tetrapeptide, a key intermediate that has been used as starting material for the synthesis of new non natural glycopeptides. One of them has shown a weak but promising activity against Van A Enterococci highly resistant to natural glycopeptides.