Xiuqing Wang, Biswajit Mishra, T. Lushnikova
May 1, 2018
Citations
0
Influential Citations
30
Citations
Journal
Advanced Biosystems
Abstract
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 Gram‐negative bacteria. By reducing the hydrophobic content, converting the broad‐spectrum GF‐17 to two narrow‐spectrum peptides (GF‐17d3 and KR‐12) with activity against Gram‐negative bacteria is successful. 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, the 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 Staphylococcus aureus USA300. These new selective peptides constitute interesting candidates for future development.