Temporin L (TL, 13-residues long) is a frog-skin peptide with a wide and potent spectrum of antimicrobial activity, but with a toxic effect on mammalian cells at its microbicidal concentration. Previous studies indicated [Pro3]TL as an analog with a slightly lower hemolytic activity than the native TL. Here, a systematic replacement of single residues within the alpha-helix domain of Pro3 TL (Lys7 to Leu13) with D aminoacids, known as helix breakers, has been carried out. Structure-activity relationship studies, by means of CD/NMR spectroscopy analysis and antimicrobial/hemolytic assays have been performed leading to a better understanding on the structural elements that are responsible for the cell selectivity of TL. Most importantly, we have found how a single L-to D aminoacid substitution can preserve the strong anti-candida activity of [Pro3]TL, making it completely harmless towards human cells.
The effect of d-amino acids in the target cell selectivity of the frog skin peptide temporin L / Luca, Vincenzo; P., Grieco; A., Carotenuto; L., Auriemma; M. R., Saviello; P., Campiglia; MARCELLINI HERCOLANI GADDI, Ludovica; Mangoni, Maria Luisa. - STAMPA. - (2012), pp. 38-38. (Intervento presentato al convegno New antimicrobial workshop - New compounds and new strategies for antimicrobials. tenutosi a Trieste nel 25-26 maggio 2012).
The effect of d-amino acids in the target cell selectivity of the frog skin peptide temporin L.
LUCA, VINCENZO;MARCELLINI HERCOLANI GADDI, LUDOVICA;MANGONI, Maria Luisa
2012
Abstract
Temporin L (TL, 13-residues long) is a frog-skin peptide with a wide and potent spectrum of antimicrobial activity, but with a toxic effect on mammalian cells at its microbicidal concentration. Previous studies indicated [Pro3]TL as an analog with a slightly lower hemolytic activity than the native TL. Here, a systematic replacement of single residues within the alpha-helix domain of Pro3 TL (Lys7 to Leu13) with D aminoacids, known as helix breakers, has been carried out. Structure-activity relationship studies, by means of CD/NMR spectroscopy analysis and antimicrobial/hemolytic assays have been performed leading to a better understanding on the structural elements that are responsible for the cell selectivity of TL. Most importantly, we have found how a single L-to D aminoacid substitution can preserve the strong anti-candida activity of [Pro3]TL, making it completely harmless towards human cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
