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-alani ne of growing peptidoglycan chains. Glycopeptides are active against G ram-positive bacteria including the major pathogens. Among all the gly copeptides 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 methicil lin-resistant Staphylococcus aureus and coagulase-negative staphylococ ci. Basic amides of teicoplanin aglycon have produced one compound end owed with interesting activity against Gram-negative bacteria because of its ability to cross the outer membrane of this last bacteria. Sele ctive degradation of teicoplanin has given a tetrapeptide, a key inter mediate that has been used as starting material for the synthesis of n ew non natural glycopeptides. One of them has shown a weak but promisi ng activity against Van A Enterococci highly resistant to natural glyc opeptides.