title: The effect of d-amino acid substitution on the selectivity of temporin L towards target cells: identification of a potent anti-Candida peptide.
abstract: The frog skin peptide temporin L (TL, 13-residues long) has a wide and potent spectrum of antimicrobial activity, but it is also toxic on mammalian cells at its microbicidal concentrations. Previous studies have indicated that its analogue [Pro(3)]TL has a slightly reduced hemolytic activity and a stable helical conformation along residues 6-13. Here, to expand our knowledge on the relationship between the extent/position of α-helix in TL and its biological activities, we systematically replaced single amino acids within the α-helical domain of [Pro(3)]TL with the corresponding d isomers, known as helix breakers. Structure-activity relationship studies of these analogues, by means of CD and NMR spectroscopy analyses as well as antimicrobial and hemolytic assays were performed. Besides increasing our understanding on the structural elements that are responsible for cell selectivity of TL, this study revealed that a single l to d amino acid substitution can preserve strong anti-Candida activity of [Pro(3)]TL, without giving a toxic effect towards human cells.
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry, University of Naples 'Federico II', I-80131 Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
authors.forename: Luigia
authors.initials: L
authors.lastname: Auriemma
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Saviello
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Gomez-Monterrey
authors.forename: Ludovica
authors.initials: L
authors.lastname: Marcellini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Luca
authors.forename: Donatella
authors.initials: D
authors.lastname: Barra
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mangoni
mesh_terms: D040981:Acinetobacter baumannii / Q000378:metabolism; D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D002175:Candida / Q000378:metabolism*; D002176:Candida albicans / Q000378:metabolism; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000378:metabolism; D005452:Fluoresceins / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008823:Micelles; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D013210:Staphylococcus / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000378:metabolism
chemical_list: D000596:Amino Acids; D023181:Antimicrobial Cationic Peptides; D005452:Fluoresceins; D008823:Micelles; D010455:Peptides; C469676:temporin L, Rana temporaria; C007740:fluorexon