Amphipathic antimicrobial peptides- from biophysics to therapeutics?

CE Dempsey, A Hawrani, RA Howe, TR Walsh

Research output: Contribution to journalArticle (Academic Journal)peer-review

23 Citations (Scopus)


Amphipathic peptides are accommodated within the diffuse gradient of polarity that characterizes the interfacial regions of phospholipid bilayer membranes. Interfacial membrane interactions are key to the diverse biological functions and activities of these peptides, which encompass a large class of antimicrobial peptides including the helical peptides magainin, melittin, and RTA3 derived from the commensal bacterium Streptococcus mitis. For these peptides in vitro efficacy (high antimicrobial activity with minimal mammalian cell toxicity, equivalent to high potential therapeutic index; PTI), can be broadly understood in relation to the thermodynamics of interfacial binding and membrane disruption in membranes having surface charges that correspond to bacterial and mammalian cell membranes, respectively. Peptides with disrupted amphipathicity resulting from a positively charged amino acid residue on the non-polar helix face, can have greatly enhanced PTI, although a balance of amphipathicity, hydrophobicity and positive charge is required for retention of high antimicrobial activity. These observations are illustrated with recent examples from the literature, and studies on RTA3 and magainin analogues from our laboratories. Despite the identification and optimisation of peptides with very good PTI, a focus on addressing toxicity upon systemic administration and poor in vivo efficacy is likely to be required to translate growing understanding of the relationships between peptide interfacial activity and effects on cells, into novel systemic therapeutics.
Translated title of the contributionAmphipathic antimicrobial peptides- from biophysics to therapeutics?
Original languageEnglish
Pages (from-to)1334 - 1344
Number of pages11
JournalProtein & Peptide Letters
Volume17 (11)
Publication statusPublished - Nov 2010

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