Rational Concepts for the Design of Novel Glycopeptides

The originally nonbiased modifications of glycopeptide molecules used in SAR studies together with the knowledge on the mode of action, stimulated researchers to develop more rational and sophisticated approaches and concepts to raise antibiotic activity of glycopeptide derivatives also against glycopeptide-resistant bacterial strains. A selection of these approaches is discussed in the subsequent sections. 

2 Glycopeptides and Glycopeptide-Based Approaches with Antibiotic Activity Against Vancomycin-Resistant Bacteria 

In another conceptually different approach, the ester hnkage of D-Ala-D-Lac of VRE was considered as a hydrolytically cleavable functional group.The screening of a nonbiased peptide library rendered an s-aminopentanoylated prolinol 

From the current view of the author, few chances remain for any more enhancement of antibiotic activity based on the derivatization with lipophilic residues. This view is also reflected by other approaches, which tested covalently tethered dimers and trimers and vancomycin-based libraries. An apparent disadvantage of the dimer approach for clinical use, however, is the relatively high molecular 

Finally, it has to be noted that glycopeptides only represent one option to combat infections by gram-positive bacteria. Current research is focused on other cell wall biosynthesis inhibitors (e.g., (3-lactams, cephalosporins) or even on the development of antibacterial agents (e.g., tetracyclines, ketohdes, and quinolone antibiotics) against other targets.An important drug candidate in this context is hnezolid (Zyvox), which is an entirely synthetic oxazolidinone antibiotic with in vitro and in vivo efficiency against MRS A and VRE.  

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