Temporins constitute a family of amphipathic alpha-helical antimicrobial peptides (AMPs) and contain some of the shortest cytotoxic peptides, comprised of only 10-14 residues. We have recently investigated two members of this family, temporin A (TA) and temporin L (TL), because of their different spectra of antimicrobial activity and toxicity. Consequently, we developed new analogues with promising biological activities named Pro(3)-TL and Gln(3)-TA. In this work, we performed a detailed NMR analysis of the new analogues in SDS and DPC micelles, which mimic bacterial and mammalian membranes, respectively. NMR studies reveal that strongly hemolytic Gln(3)-TA was in a stable helical conformation along the entire sequence, while weakly hemolytic but antimicrobial Pro(3)-TL showed conformational averaging at the N-terminus. Furthermore, molecular dynamics (MD) simulations on TL and Pro(3)-TL were performed in explicit water and DPC micelles. Simulations indicated that both peptides prefer a location at the micelle-water interface; however, Phe(1) of strongly hemolytic TL was embedded more in depth into DPC, and only TL caused a significant distortion of the micelle shape. By combining NMR and computational analyses, we obtained a molecular-level resolution of the interactions between TL and its analogues with membrane mimicking micelles

New Insight into the Mechanism of Action of the Temporin Antimicrobial Peptides

GRIECO, PAOLO;NOVELLINO, ETTORE;CAROTENUTO, ALFONSO
2010

Abstract

Temporins constitute a family of amphipathic alpha-helical antimicrobial peptides (AMPs) and contain some of the shortest cytotoxic peptides, comprised of only 10-14 residues. We have recently investigated two members of this family, temporin A (TA) and temporin L (TL), because of their different spectra of antimicrobial activity and toxicity. Consequently, we developed new analogues with promising biological activities named Pro(3)-TL and Gln(3)-TA. In this work, we performed a detailed NMR analysis of the new analogues in SDS and DPC micelles, which mimic bacterial and mammalian membranes, respectively. NMR studies reveal that strongly hemolytic Gln(3)-TA was in a stable helical conformation along the entire sequence, while weakly hemolytic but antimicrobial Pro(3)-TL showed conformational averaging at the N-terminus. Furthermore, molecular dynamics (MD) simulations on TL and Pro(3)-TL were performed in explicit water and DPC micelles. Simulations indicated that both peptides prefer a location at the micelle-water interface; however, Phe(1) of strongly hemolytic TL was embedded more in depth into DPC, and only TL caused a significant distortion of the micelle shape. By combining NMR and computational analyses, we obtained a molecular-level resolution of the interactions between TL and its analogues with membrane mimicking micelles
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/364353
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 41
  • ???jsp.display-item.citation.isi??? 37
social impact