Journal
AMINO ACIDS
Volume 48, Issue 2, Pages 403-417Publisher
SPRINGER WIEN
DOI: 10.1007/s00726-015-2094-y
Keywords
Mirror-like peptides; Rational design; Alanine regulation; Cell selectivity; Bactericidal; mechanism
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Funding
- National Science and Technology Support Program [BAD10B03]
- National Natural Research Foundation of China [31272453, 31472104]
- National Basic Research Program [2012CB124703]
- China Agriculture Research System [CARS-36]
- Program of Ministry of Education of China [20092325110009]
- Key Research Program of Heilongjiang Education Bureau [1254CGZH22, 11551z003]
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To generate effective antimicrobial peptides (AMPs) with good antimicrobial activities and cell selectivity, many synthetic strategies have been implemented to facilitate the development of AMPs. However, these synthetic strategies represent only a small proportion of the methods used for the development of AMPs and are not optimal with the requirements needed for the design of AMPs. In this investigation, we designed a mirror-like structure with a lower charge and a higher number of hydrophobic amino acids. The amino acid sequence of the designed mirror-like peptides was XXYXXXYXXXYXX [X represents L (Leu) and/or A (Ala); Y represents K (Lys)]. These mirror-like peptides displayed antimicrobial activity against both Gram-positive and Gram-negative bacteria. Hemolysis activity and cytotoxicity, detected by using human red blood cells (hRBCs) and human embryonic kidney cells (HEK293), respectively, demonstrated that the frequency of Ala residues in this structure had a regulatory effect on the high hydrophobic region. In particular, KL(4)A(6) showed a greater antimicrobial potency than the other three mirror-like peptides, folded into an alpha-helical structure, and displayed the highest therapeutic index, suggesting its good cell selectivity. Observations from fluorescence spectroscopy, flow cytometry, and electron microscopy experiments indicated that KL(4)A(6) exhibited good membrane penetration potential by inducing membrane blebbing, disruption and lysis. Therefore, generating mirror-like peptides is a promising strategy for designing effective AMPs with regions of high hydrophobicity.
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