Matching amino acids membrane preference profile to improve activity of antimicrobial peptides

초록

Canonical helical antimicrobial peptides are less insertive and less active. Here, an improved antimicrobial peptide, WCopWs, indicate that matching amino acids membrane preference profile improves insertion and activity. Antimicrobial peptides (AMPs) are cationic antibiotics that can kill multidrug-resistant bacteria via membrane insertion. However, their weak activity limits their clinical use. Ironically, the cationic charge of AMPs is essential for membrane binding, but it obstructs membrane insertion. In this study, we postulate that this problem can be overcome by locating cationic amino acids at the energetically preferred membrane surface. All amino acids have an energetically preferred or less preferred membrane position profile, and this profile is strongly related to membrane insertion. However, most AMPs do not follow this profile. One exception is protegrin-1, a powerful but neglected AMP. In the present study, we found that a potent AMP, WCopW5, strongly resembles protegrin-1 and that the match between its sequence and the preferred position profile closely correlates with its antimicrobial activity. One of its derivatives, WCopW43, has antimicrobial activity comparable to that of the most effective AMPs in clinical use.

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