[Glycopeptide antibiotics resistance mechanism as the basis for novel derivatives development capable to overcome...

The data on the genetic and biochemical bases of bacterial resistance to antibiotics of the vancomycin-ristocetin group are summarized. Special emphasis is placed on the mechanism of resistance associated with target modification and on molecular interactions occurring upon contact of glycopeptides with normal and modified targets. The prospects for developing new derivatives active against resistant bacteria are discussed. The most rational approach to the chemical transformation of glycopeptides involves the modification of the internal "binding pocket" and the peripheral regions of the molecule that participate in the stabilization of the antibiotic-target complex. Novel semisynthetic drugs of this group active against glycopeptide-resistant enterococci are described.