期刊
CURRENT MEDICINAL CHEMISTRY
卷 27, 期 9, 页码 1405-1419出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867326666190722095408
关键词
Antimicrobial peptides; Pseudomonas aeruginosa; innate immunity; gold nanoparticles; contact lenses; D-amino acids; wound healing
资金
- Sapienza University of Rome [RM116154C8434109, RM11816436113D8A]
- Italian Cystic Fibrosis Foundation [FFC 15/2017]
Antimicrobial Peptides (AMPs) are the 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 diastercomer 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 AMPs to the direction of peptide-based drugs for clinical use.
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