Cationic antimicrobial peptides in clinical development, with special focus on thanatin and heliomicin

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Abstract

Cationic host-defence antimicrobial peptides are recognised as an important component of the innate immune response in most multicellular organisms. In humans, several antimicrobial peptides have recently been recognised as key factors in the pathology of diseases such as cystic fibrosis, septic shock, atopic dermatitis and morbus Kostmann. To date, several hundred cationic antimicrobial peptides have been characterised. They are amphipathic peptides, comprising 20 to 50 amino acids, and exhibiting large structural diversity. These peptides display a broad spectrum of activity against bacterial, fungal and viral pathogens. Their mode of action is best known for cecropins and magainins, which act upon the cytoplasmic membrane of microorganisms, causing its disruption by a detergent-like activity and pore formation. In the last few years, several of these peptides or analogues (derived from magainin, protegrin, indolicidin and histatin) were in advanced clinical development, especially for localised infections (oral and cutaneous infections, pneumonias etc.). Several other molecules (rBPI, heliomicin and thanatin) are currently under development for various systemic infections (Staphylococcus sp., Aspergillus sp., Candida sp. etc.) and may represent important additions to the anti-infectious therapeutic arsenal.