Novel antimicrobial self-assembled cyclic peptide nanotubes containing (1R,3S,4R,5R)-3-amino-4,5-dihydroxycyclohexane-1-carboxylic acid, a new building block for developing mimetics of saccharide–peptide hybrids

Abstract

A new class of supramolecular antimicrobials based on D,L-cyclic peptides containing a dihydroxylated-γ-residue, which was designed to mimic the saccharide component present in certain carbohydrate–peptide hybrids, is described. The fully protected amino acid was prepared from shikimic acid and incorporated into clickable amphipathic cyclic peptides. The resulting peptides self-assemble into nanotubes that interact with bacterial membranes, ultimately causing cell death. Notably, the incorporation of this new residue not only retains antimicrobial activity but also significantly reduces toxicity in mammalian cells, thereby broadening the therapeutic window of these peptides.