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Amphiphilic tobramycin analogues with potent antibacterial activity against tobramycin‐resistant bacteria were synthesized. Most analogues were found to be less prone to deactivation by aminoglycoside‐modifying enzymes than tobramycin. These compounds target the bacterial membrane rather than the ribosome (see picture). The lipophilic residue of these analogues is key to their antibacterial potency and selectivity towards bacterial membranes.

Galectin-8, a member of the galectin family of mammalian lectins, is made of two carbohydrate-recognition domains (CRDs), joined by a "hinge" region. Ligation of integrins by galectin-8 induces a distinct cytoskeletal organization, associated with activation of the extracellular-regulated kinase (ERK) and phosphatidylinositol 3-kinase signaling cascades. We show that these properties of galectin-8 are mediated by the concerted action of its two CRDs and involve both protein-sugar and protein-protein interactions. Accordingly, the isolated N- or C-CRD domains of galectin-8 or galectin-8 mutated at selected residues implicated in sugar binding (E251Q; W85Y, W248Y, W[85,248]Y) exhibited reduced sugar binding, which was accompanied by severe impairment in the capacity of these mutants to promote the adhesive, spreading, and signaling functions of galectin-8. Other mutations that did not impair sugar binding (e.g. E88Q) still impeded the signaling and cell-adherence functions of galectin-8. Deletion of the "hinge" region similarly impaired the biological effects of galectin-8. These results provide evidence that cooperative interactions between the two CRDs and the "hinge" domain are required for the proper functioning of galectin-8.

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Amphiphile Analoga von Tobramycin wurden synthetisiert, die gegen tobramycinresistente Bakterien wirken. Die meisten Derivate waren weniger anfällig für eine Desaktivierung durch Aminoglycoside modifizierende Enzyme als Tobramycin. Diese Verbindungen zielen auf die Bakterienmembran ab und nicht auf das Ribosom (siehe Bild). Der lipophile Rest dieser Analoga ist entscheidend für ihre antibakterielle Wirksamkeit und ihre Selektivität für bakterielle Membranen.

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Amphiphile Aminoglycosid‐Antibiotika töten Bakterien durch Zerstörung ihrer hoch negativ geladenen Membran. In der Zuschrift auf beschreiben M. Fridman, S. Garneau‐Tsodikova et al. 6′′‐Thioether‐Tobramycin‐Derivate und zeigen, dass deren aliphatische Kette wie ein Bohrer wirkt, der Bakterienzellen aufbrechen kann. Diese wirksamen Verbindungen umgehen viele der gewöhnlichen bakteriellen Abwehrmechanismen und ebnen so einen neuen Weg für die Erforschung von Antibiotika, die die Membran angreifen.