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Rational design of mirror-like peptides with alanine regulation.

Authors :
Li, Weizhong
Tan, Tingting
Xu, Wei
Xu, Lin
Dong, Na
Ma, Deying
Shan, Anshan
Source :
Amino Acids. Feb2016, Vol. 48 Issue 2, p403-417. 15p.
Publication Year :
2016

Abstract

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 XXYXXXY XXXYXX [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, KLA showed a greater antimicrobial potency than the other three mirror-like peptides, folded into an α-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 KLA 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09394451
Volume :
48
Issue :
2
Database :
Academic Search Index
Journal :
Amino Acids
Publication Type :
Academic Journal
Accession number :
112693461
Full Text :
https://doi.org/10.1007/s00726-015-2094-y