Salt sensitivity of antimicrobial peptides poses a major obstacle in their development as
novel antibiotics. Here we report the use of helix-capping motifs to confer salt resistance
upon helical antimicrobial peptides. The helical content of the template peptide [RLLR] 5
was almost completely destroyed at salt concentrations over 200 mm NaCl, leading to a 8–
32-fold decrease in antimicrobial activity. However, the introduction of helix-capping motifs
at the helix termini resulted in a structurally stable peptide, which retained membrane …