Title:The Potential of Frog Skin Peptides for Anti-Infective Therapies: The Case of Esculentin-1a(1-21)NH2
Volume: 27
Issue: 9
关键词:
抗菌肽，铜绿假单胞菌，先天免疫，金纳米颗粒，隐形眼镜，D-氨基酸，伤口愈合。
摘要: 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 diastereomer carrying Damino
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.
