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Bulky nonproteinogenic amino acids permit the design of very small and effective cationic antibacterial peptides.

The rate of multidrug-resistant infections is rapidly rising. Cationic antibacterial peptides are active against resistant pathogens and have low propensity for resistance development, but because of their unfavorable medicinal properties, cationic antibacterial peptides have been a limited clinical success. We have found that introduction of nongenetically coded amino acids and other lipophilic modifications opens the opportunity for development of extremely short and highly active antibacterial peptides with improved medicinal properties.