| Summary: | For some time, glycopeptide antibiotics have been considered the last line of defense against Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). However, vancomycin resistance of Gram-positive bacteria is an increasingly emerging worldwide health problem. The mode of action of glycopeptide antibiotics is essentially the binding of peptidoglycan cell-wall fragments terminating in the <span style="font-variant: small-caps;">d</span>-Ala-<span style="font-variant: small-caps;">d</span>-Ala sequence to the carboxylate anion binding pocket of the antibiotic. Dimerization of these antibiotics in aqueous solution was shown to persist and even to enhance the antibacterial effect in a co-operative manner. Some works based on solid state (ss) Nuclear Magnetic Resonance (NMR) studies questioned the presence of dimers under the conditions of ssNMR while in a few cases, higher-order oligomers associated with contiguous back-to-back and face-to-face dimers were observed in the crystal phase. However, it is not proved if such oligomers persist in aqueous solutions. With the aid of <sup>15</sup>N-labelled eremomycin using <sup>15</sup>N relaxation and diffusion NMR methods, we observed tetramers and octamers when the <i>N</i>-Ac-<span style="font-variant: small-caps;">d</span>-Ala-<span style="font-variant: small-caps;">d</span>-Ala dipeptide was added. To the contrary, the <i>N</i>-Ac-<span style="font-variant: small-caps;">d</span>-Ala or (<i>N</i>-Ac)<sub>2</sub>-<span style="font-variant: small-caps;">l</span>-Lys-<span style="font-variant: small-caps;">d</span>-Ala-<span style="font-variant: small-caps;">d</span>-Ala tripeptide did not induce higher-order oligomers. These observations are interesting examples of tailored supramolecular self-organization. New antimicrobial tests have also been carried out with these self-assemblies against MRSA and VRE (resistant) strains.
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