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Technology

This technology uses a computer-aided evolutionary genetic algorithm driven by a fitness function to generate synthetic peptides with optimized antimicrobial function. The program uses an AMP sequence that exists in nature to generate new variants by performing virtual crossing over and substitution mutations, and then the program selects the ‘fittest’ AMP variants. Several iterations of these steps are performed then the top solutions can be synthesized for in vitro and in vivo testing. As proof of principle, the inventors used this in silico design tool to generate artificial AMPs, called guavanins, derived from the guava peptide Pg-AMP1. The guavanins designed using this computational tool displayed improved antibiotic potency against the Gram-negative bacteria P. aeruginosa, E. coli, and A. baumannii, and were additionally less toxic to human cells than the parent compound. In a mouse skin infection model, the lead guavanin compound led to a thousand-fold reduction in P. aeruginosa compared to the parent molecule. In conclusion, this computer-aided design platform is a promising new tool for generating novel AMPs with improved therapeutic properties.