Structure-activity study of the antibacterial peptide fallaxin

Fallaxin is a 25-mer antibacterial peptide amide, which was recently isolated from the West Indian mountain chicken frog Leptodactylus fallax. Fallaxin has been shown to inhibit the growth of several Gram-negative bacteria including Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Here, we report a structure-activity study of fallaxin based on 65 analogs, including a complete alanine scan and a full set of N- and C-terminal truncated analogs. The fallaxin analogs were tested for hemolytic activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant S. aureus, (VISA), methicillin-susceptible S. aureus (MSSA), E. coli, K. pneumoniae, and P. aeruginosa. We identified several analogs, which showed improved antibacterial activity compared to fallaxin. Our best candidate was FA12, which displayed MIC values of 3.12, 25, 25, and 50 µM against E. coli, K. pneumoniae, MSSA, and VISA, respectively. Furthermore, we correlated the antibacterial activity with various structural parameters such as charge, hydrophobicity <img src="http://www.proteinscience.org/math/lang.gif" alt="<" style="width: 4px; height: 15px; border-width: 0px"/>H<img src="http://www.proteinscience.org/math/rang.gif" alt=">" style="width: 4px; height: 15px; border-width: 0px"/>, mean hydrophobic moment <img src="http://www.proteinscience.org/math/lang.gif" alt="<" style="width: 4px; height: 15px; border-width: 0px"/>µH<img src="http://www.proteinscience.org/math/rang.gif" alt=">" style="width: 4px; height: 15px; border-width: 0px"/>, and <img src="http://w