Open AccessAmino Acid Composition Determines Peptide Activity Spectrum and Hot‐Spot‐Based Design of Merecidin
Author(s) -
Wang Xiuqing,
Mishra Biswajit,
Lushnikova Tamara,
Narayana Jayaram Lakshmaiah,
Wang Guangshun
Publication year - 2018
Publication title -
advanced biosystems
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.153
H-Index - 18
ISSN - 2366-7478
DOI - 10.1002/adbi.201700259
Subject(s) - antimicrobial , peptide , cathelicidin , antimicrobial peptides , bacteria , amino acid , pathogenic bacteria , biology , galleria mellonella , staphylococcus aureus , biochemistry , microbiology and biotechnology , chemistry , virulence , genetics , gene
There is a great interest in developing the only human cathelicidin into therapeutic molecules. The major antimicrobial region of human LL-37 corresponds to residues 17-32. The resultant peptide GF-17 shows a broad spectrum of antimicrobial activity against both Gram-positive and negative bacteria. By reducing the hydrophobic content, we previously succeeded in converting the broad-spectrum GF-17 to two narrow-spectrum peptides (GF-17d3 and KR-12) with activity against Gram-negative bacteria. This study demonstrates that substitution of multiple basic amino acids by hydrophobic alanines makes a broad-spectrum peptide 17BIPHE2 (designed based on GF-17d3) active against Staphylococcal pathogens but not other bacteria tested. Taken together, our results reveal distinct charge and hydrophobic requirements for peptides to kill Gram-positive or Gram-negative bacteria. This finding is in line with the bioinformatics analysis of the peptides in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). In addition, a hot spot arginine is identified and used to design merecidin with reduced toxicity to human cells. Merecidin protects wax moth larvae ( Galleria mellonella ) from the infection of methicillin-resistant S. aureus USA300. These new selective peptides constitute interesting candidates for future development.