title: Alanine scanning analysis and structure-function relationships of the frog-skin antimicrobial peptide temporin-1Ta.
abstract: The increasing resistance of bacteria and fungi to the available antibiotic/antimycotic drugs urges for a search for new anti-infective compounds with new modes of action. In line of this, natural CAMPs represent promising and attractive candidates. Special attention has been devoted to frog-skin temporins, because of their short size (10-14 residues long) and their unique features. In particular, temporin-1Ta has the following properties: (i) it is mainly active on Gram-positive bacteria; (ii) it can synergize, when combined with temporin-1Tl, in inhibiting both gram-negative bacterial growth and the toxic effect of LPS; (iii) it preserves biological activity in the presence of serum; and (iv) it is practically not hemolytic. Rational design of CAMPs represents a straightforward approach to obtain a peptide with a better therapeutic index. Here, we used alanine scanning analogs to elucidate the contribution of the side chains of each amino acid residue to the peptide's antimicrobial and hemolytic activity. Beside providing insight into the biophysical attributes and the critical positions within the peptide sequence, which govern the antimicrobial/hemolytic activity of this temporin isoform, our studies assist in optimizing the design of temporin-based lead structures for the production of new anti-infective agents.
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: Vincenzo
authors.initials: V
authors.lastname: Luca
authors.forename: Luigia
authors.initials: L
authors.lastname: Auriemma
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Saviello
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
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: D029845:Amphibian Proteins / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D006461:Hemolysis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011898:Ranidae; D012867:Skin / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D029845:Amphibian Proteins; D000890:Anti-Infective Agents; C514607:temporin-1TGa, Rana tagoi