title: Antifungal peptides at membrane interaction.
abstract: Many drugs are available for the treatment of systemic or superficial mycoses, but only a limited number of them are effective antifungal drugs, devoid of toxic and undesirable side effects. Furthermore, resistance development and fungistatic rather than fungicidal activities represent limitations of current antifungal therapy. Therefore an urgent need for a new generation of antifungal agents remains. We recently synthesised a set of linear and cyclic peptides characterized by sequences typical of membrane-active antimicrobial peptides (AMP). AMT2, cyclo-AMT2, AMT3 and cyclo-AMT3 (Scheme 1) were tested against different yeast species and exhibited general antifungal activity, with a specificity against Cryptococcus neoformans. To evaluate the role of the membrane cell in the mechanism of antifungal activity, we investigated the conformational behaviour of AMT2, cyclo-AMT2, AMT3 and cyclo-AMT3 in different bio-membrane mimicking systems using a combined approach based on spectroscopy and microscopy techniques. Our data highlight the behaviour of the peptides to interact with the bilayer surface, excluding their ability to destabilize or permeabilize the fungal cell wall. Microbial membrane, indeed, may be an important platform for specific interactions of peptides with specific targets involved in the cell wall synthesis.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Salerno, Via Ponte Don Melillo 8, 84024 Fisciano (SA), Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Di Marino
authors.forename: Mario
authors.initials: M
authors.lastname: Scrima
authors.forename: Manuela
authors.initials: M
authors.lastname: Grimaldi
authors.forename: Gerardino
authors.initials: G
authors.lastname: D'Errico
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vitiello
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.forename: Margherita
authors.initials: M
authors.lastname: De Rosa
authors.forename: Annunziata
authors.initials: A
authors.lastname: Soriente
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000166:cytology / Q000187:drug effects; D008051:Lipid Bilayers / Q000378:metabolism; D008958:Models, Molecular; D010539:Permeability; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers