To overcome vancomycin resistance both dual D-Ala-D-Ala/D-Ala-D-Lac binding derivatives , and lipo-glycopeptides derivatives have been synthesized . Lipo-glycopeptides display a dual mechanism of action, blocking peptidoglycan synthesis and causing membrane depolarization . The membrane activity of lipoglycopeptides is conferred by a lipophilic tail attached to the typical glycopeptide scaffold . The tail can be either aliphatic (Telavancin, Dalbavancin) or with aromatic rings (Oritavancin). This tail enables the lipo-glycopeptides to anchor into the bacterial membrane, providing a concentrating effect that enhances both the disruption of peptidoglycan synthesis and membrane depolarization. The dual mechanism of action allows to overcome vancomycin resistance and makes lipo-glycopeptides highly effective in clinical settings and less susceptible to the emergence of other resistance mechanisms [133].