Host defense peptides selectively kill bacterial and cancer cells (including those that are drug-resistant) by perturbing the permeability of their membranes, without being significantly toxic to the host. Coulombic interactions between these cationic and amphipathic peptides and the negatively charged membranes of pathogenic cells contribute to the selective toxicity. However, a positive charge is not sufficient for selectivity, which can be achieved only by a finely tuned balance of electrostatic and hydrophobic driving forces. A common property of amphipathic peptides is the formation of aggregated structures in solution, but the role of this phenomenon in peptide activity and selectivity has received limited attention. Our data on the anticancer peptide killerFLIP demonstrate that aggregation strongly increases peptide selectivity, by reducing the effective peptide hydrophobicity and thus the affinity towards membranes composed of neutral lipids (like the outer layer of healthy eukaryotic cell membranes). Aggregation is therefore a useful tool to modulate the selectivity of membrane active peptides and peptidomimetics.

Aggregation determines the selectivity of membrane-active anticancer and antimicrobial peptides: the case of killerFLIP / Vaezi, Zahra; Bortolotti, Annalisa; Luca, Vincenzo; Perilli, Giulia; Mangoni, Maria Luisa; Khosravi-Far, Roya; Bobone, Sara; Stella, Lorenzo. - In: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES. - ISSN 0005-2736. - (2020), p. 183107. [10.1016/j.bbamem.2019.183107]

Aggregation determines the selectivity of membrane-active anticancer and antimicrobial peptides: the case of killerFLIP

Luca, Vincenzo;Mangoni, Maria Luisa;
2020

Abstract

Host defense peptides selectively kill bacterial and cancer cells (including those that are drug-resistant) by perturbing the permeability of their membranes, without being significantly toxic to the host. Coulombic interactions between these cationic and amphipathic peptides and the negatively charged membranes of pathogenic cells contribute to the selective toxicity. However, a positive charge is not sufficient for selectivity, which can be achieved only by a finely tuned balance of electrostatic and hydrophobic driving forces. A common property of amphipathic peptides is the formation of aggregated structures in solution, but the role of this phenomenon in peptide activity and selectivity has received limited attention. Our data on the anticancer peptide killerFLIP demonstrate that aggregation strongly increases peptide selectivity, by reducing the effective peptide hydrophobicity and thus the affinity towards membranes composed of neutral lipids (like the outer layer of healthy eukaryotic cell membranes). Aggregation is therefore a useful tool to modulate the selectivity of membrane active peptides and peptidomimetics.
2020
aggregation; fective hydrophobicity; host defense peptides; toxicity
01 Pubblicazione su rivista::01a Articolo in rivista
Aggregation determines the selectivity of membrane-active anticancer and antimicrobial peptides: the case of killerFLIP / Vaezi, Zahra; Bortolotti, Annalisa; Luca, Vincenzo; Perilli, Giulia; Mangoni, Maria Luisa; Khosravi-Far, Roya; Bobone, Sara; Stella, Lorenzo. - In: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES. - ISSN 0005-2736. - (2020), p. 183107. [10.1016/j.bbamem.2019.183107]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1336111
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