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Abstract Gram-negative bacteria possess intrinsic resistance to glycopeptide antibiotics so these important antibacterial medications are only suitable for the treatment of Gram-positive bacterial infections. At the same time, polymyxins are peptide antibiotics, structurally related to glycopeptides, with remarkable activity against Gram-negative bacteria. With the aim of breaking the intrinsic resistance of Gram-negative bacteria against glycopeptides, a polycationic vancomycin aglycone derivative carrying an n-decanoyl side chain and five aminoethyl groups, which resembles the structure of polymyxins, was prepared. Although the compound by itself was not active against the Gram-negative bacteria tested, it synergized with teicoplanin against Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii, and it was able to potentiate vancomycin against these Gram-negative strains. Moreover, it proved to be active against vancomycin- and teicoplanin-resistant Gram-positive bacteria.