The search of antimicrobial peptides (AMP) as candidates for the development of antibiotics is an active research field. In this paper we investigated the role of charged residues in antimicrobial activity by using as a template the previously characterized crabrolin peptide. Mutant peptides in which the charge was diminished (Crabrolin Minus) or increased (Crabrolin Plus) were assayed for their ability to inhibit bacterial growth and to bind model bacterial membranes or lipopolysaccharide (LPS). Structural analysis of both peptides by means of CD, NMR and Molecular Dynamics was also performed and correlated to the biological data. Although native Crabrolin (WT) displays smaller efficacy than other antibacterial peptides with similar length, Crabrolin Plus displays a significant antimicrobial activity while Crabrolin Minus is not active, thus confirming the key role of the positive charge for interacting with the bacterial membrane. Moreover, our results show that charge position has no effect on the helical propensity of the peptides but drastically affects their antimicrobial activity. Antimicrobial activity versus Gram-positive and Gram-negative bacteria, as well as specific interaction with LPS, suggest multiple binding modes for the active peptide.

Aschi, M., Perini, N., Bouchemal, N., Luzi, C., Savarin, P., Migliore, L., et al. (2019). Structural characterization and biological activity of Crabrolin peptide isoforms with different positive charge. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES [10.1016/j.bbamem.2019.183055].

Structural characterization and biological activity of Crabrolin peptide isoforms with different positive charge

Perini N;Migliore L;Sette M.
2019-01-01

Abstract

The search of antimicrobial peptides (AMP) as candidates for the development of antibiotics is an active research field. In this paper we investigated the role of charged residues in antimicrobial activity by using as a template the previously characterized crabrolin peptide. Mutant peptides in which the charge was diminished (Crabrolin Minus) or increased (Crabrolin Plus) were assayed for their ability to inhibit bacterial growth and to bind model bacterial membranes or lipopolysaccharide (LPS). Structural analysis of both peptides by means of CD, NMR and Molecular Dynamics was also performed and correlated to the biological data. Although native Crabrolin (WT) displays smaller efficacy than other antibacterial peptides with similar length, Crabrolin Plus displays a significant antimicrobial activity while Crabrolin Minus is not active, thus confirming the key role of the positive charge for interacting with the bacterial membrane. Moreover, our results show that charge position has no effect on the helical propensity of the peptides but drastically affects their antimicrobial activity. Antimicrobial activity versus Gram-positive and Gram-negative bacteria, as well as specific interaction with LPS, suggest multiple binding modes for the active peptide.
2019
In corso di stampa
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
Antimicrobial peptides; Crabrolin; Nuclear magnetic resonance; Circular dichroism; Molecular dynamics
https://www.sciencedirect.com/science/article/pii/S0005273619302019?via=ihub
Aschi, M., Perini, N., Bouchemal, N., Luzi, C., Savarin, P., Migliore, L., et al. (2019). Structural characterization and biological activity of Crabrolin peptide isoforms with different positive charge. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES [10.1016/j.bbamem.2019.183055].
Aschi, M; Perini, N; Bouchemal, N; Luzi, C; Savarin, P; Migliore, L; Bozzi, A; Sette, M
Articolo su rivista
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/2108/221941
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 9
social impact