Here we report the design of membrane-active peptidomimetic molecules with a tunable arrangement of hydrophobic and polar groups. In spite of having the same chemical composition, the effective hydrophobicities of the compounds were different as a consequence of their chemical structure and conformational properties. The compound with lower effective hydrophobicity demonstrated antibacterial activity that was highly selective towards bacteria over mammalian cells. This study, highlighting the role in membrane selectivity of the specific arrangement of the different moieties in the molecular structure, provides useful indications for developing non-toxic antibacterial agents.
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