Antimicrobial peptides (AMPs) are key effectors of the innate immunity and represent promising molecules for the development of new antibacterial drugs. However, to achieve this goal, some problems need to be overcome: (i) the cytotoxic effects at high concentrations; (ii) the poor biostability and (iii) the difficulty in reaching the target site. Frog skin is one of the richest natural storehouses of AMPs and over the years, many peptides have been isolated from it, characterized and classified into several families encompassing temporins, brevinins, nigrocins and esculentins. In this review, we summarized how the isolation/characterization of peptides belonging to the esculentin-1 family drove us to the design of an analogue, i.e. esculentin-1a(1-21)NH2, with a powerful antimicrobial action and immunomodulatory properties. The peptide had a wide spectrum of activity, especially against the opportunistic Gram-negative bacterium Pseudomonas aeruginosa. We described the structural features and the in vitro/in vivo biological characterization of this peptide as well as the strategies used to improve its biological properties. Among them: (i) the design of a diastereomer carrying D-amino acids in order to reduce the peptide's cytotoxicity and improve its half-life; (ii) the covalent conjugation of the peptide to gold nanoparticles or its encapsulation into poly(lactide- co-glycolide) nanoparticles; and (iii) the peptide immobilization to biomedical devices (such as silicon hydrogel contact lenses) to obtain an antibacterial surface able to reduce microbial growth and attachment. Summing up the best results obtained so far, this review traces all the steps that led these frog-skin AMPsto the direction of peptide-based drugs for clinical use.

The potential of frog skin peptides for anti-infective therapies: the case of esculentin-1a(1-21)nh2 / Casciaro, Bruno; Cappiello, Floriana; Loffredo, Maria Rosa; Ghirga, Francesca; Mangoni, Maria Luisa. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - 27:9(2020), pp. 1405-1419. [10.2174/0929867326666190722095408]

The potential of frog skin peptides for anti-infective therapies: the case of esculentin-1a(1-21)nh2

Casciaro, Bruno
;
Cappiello, Floriana;Loffredo, Maria Rosa;Ghirga, Francesca;Mangoni, Maria Luisa
2020

Abstract

Antimicrobial peptides (AMPs) are key effectors of the innate immunity and represent promising molecules for the development of new antibacterial drugs. However, to achieve this goal, some problems need to be overcome: (i) the cytotoxic effects at high concentrations; (ii) the poor biostability and (iii) the difficulty in reaching the target site. Frog skin is one of the richest natural storehouses of AMPs and over the years, many peptides have been isolated from it, characterized and classified into several families encompassing temporins, brevinins, nigrocins and esculentins. In this review, we summarized how the isolation/characterization of peptides belonging to the esculentin-1 family drove us to the design of an analogue, i.e. esculentin-1a(1-21)NH2, with a powerful antimicrobial action and immunomodulatory properties. The peptide had a wide spectrum of activity, especially against the opportunistic Gram-negative bacterium Pseudomonas aeruginosa. We described the structural features and the in vitro/in vivo biological characterization of this peptide as well as the strategies used to improve its biological properties. Among them: (i) the design of a diastereomer carrying D-amino acids in order to reduce the peptide's cytotoxicity and improve its half-life; (ii) the covalent conjugation of the peptide to gold nanoparticles or its encapsulation into poly(lactide- co-glycolide) nanoparticles; and (iii) the peptide immobilization to biomedical devices (such as silicon hydrogel contact lenses) to obtain an antibacterial surface able to reduce microbial growth and attachment. Summing up the best results obtained so far, this review traces all the steps that led these frog-skin AMPsto the direction of peptide-based drugs for clinical use.
D-amino acids; pseudomonas aeruginosa; antimicrobial peptides; contact lenses; gold nanoparticles; innate immunity; wound healing
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
The potential of frog skin peptides for anti-infective therapies: the case of esculentin-1a(1-21)nh2 / Casciaro, Bruno; Cappiello, Floriana; Loffredo, Maria Rosa; Ghirga, Francesca; Mangoni, Maria Luisa. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - 27:9(2020), pp. 1405-1419. [10.2174/0929867326666190722095408]
File allegati a questo prodotto
File Dimensione Formato  
Casciaro_The-potential_2020.pdf

solo gestori archivio

Tipologia: Documento in Post-print (versione successiva alla peer review e accettata per la pubblicazione)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.21 MB
Formato Adobe PDF
1.21 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

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/11573/1321306
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 13
social impact