Park, IY Cho, JH Kim, KS Kim, YB Kim, MS Kim, SC 2024-01-21T07:13:49Z 2024-01-21T07:13:49Z 2021-09-02 2004-04 0021-9258 https://pubs.kist.re.kr/handle/201004/137733 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-permeabilizing and antimicrobial activities upon exposure to salt. Furthermore, the peptide with helix-capping motifs directly inhibited the in vivo growth of Streptococcus pyogenes, which causes localized fasciitis in mice, and prevented the necrosis of the epidermis, dermis, and subcutaneous muscle layers. Results indicate that the adoption of helix-capping motifs into salt-sensitive antimicrobial peptides provides the necessary structural stability for the peptides to permeabilize cell membranes and cause cell death at physiological salt concentrations. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC Helix stability confers salt resistance upon helical antimicrobial peptides Article 10.1074/jbc.M311418200 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.279, no.14, pp.13896 - 13901 JOURNAL OF BIOLOGICAL CHEMISTRY 279 14 13896 13901 N scie scopus 000220478500076 2-s2.0-1842639632 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article ESCHERICHIA-COLI BUFORIN II MECHANISM MEMBRANE MODEL ANTIBIOTICS Antimicrobial peptide Helix stability Salt resistance