title: Structure-activity relationship, conformational and biological studies of temporin L analogues.
abstract: Temporins are naturally occurring peptides with promising features, which could lead to the development of new drugs. Temporin-1Tl (TL) is the strongest antimicrobial peptide, but it is toxic on human erythrocytes and this fact makes the design of synthetic analogues with a higher therapeutic index vital.We studied the structure-activity relationships of a library of TL derivatives focusing on the correlation between the α-helix content of the peptides, the nature of their cationic residues, and their antibacterial/antiyeast/hemolytic activities. We found that the percentage of helicity of TL analogues is directly correlated to their hemolytic activity but not to their antimicrobial activity. In addition, we found that the nature of positively charged residues can affect the biological properties of TL without changing the peptide's helicity. It is noteworthy that a single amino acid substitution can prevent the antimicrobial activity of TL, making it a lytic peptide presumably due to its self-association. Last, we identified a novel analogue with properties that make it an attractive topic for future research.
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Via D Montesano 49, I-80131 Naples, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mangoni
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
authors.initials: I
authors.lastname: Gomez-Monterrey
authors.forename: Stefania
authors.initials: S
authors.lastname: Malfi
authors.forename: Ludovica
authors.initials: L
authors.lastname: Marcellini
authors.forename: Donatella
authors.initials: D
authors.lastname: Barra
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002942:Circular Dichroism; D006461:Hemolysis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D029845:Amphibian Proteins; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C469676:temporin L, Rana temporaria