Clinical Development of Cationic Antimicrobial Peptides: From Natural to Novel Antibiotics

Abstract

Over the past decade, levels of bacterial resistance to antibiotics have risen dramatically and "superbugs" resistant to most or all available agents have appeared in the clinic. Thus there is a growing need to discover and introduce new drugs. One potential source of novel antibiotics is the cationic antimicrobial peptides, which have been isolated from most living entities as components of their non-specific defenses against infectious organisms. Based on these natural templates, scores of structurally diverse antimicrobial cationic peptides have been designed, manufactured both chemically and biologically, and tested for activity against specific pathogens. A few of these peptide antibiotics have entered clinical trials to date, with mixed success. However, their diverse portfolio of structures, activity spectra, biological activities, and modes of action, provide substantial potential.

Vitamin D3 induces expression of human cathelicidin antimicrobial peptide 18 in newborns

“…Cationic antimicrobial peptides, including a-defensin, cathelicidin, and NGAL, play important roles in this system. Some of these peptides have been commercially developed as natural antibiotics [54,55]. External administration or up-regulation of endogenous hCAP18 expression by VD in neonates is a potential prophylactic or therapeutic approach, contributing to the decrease of severe bacterial infection among neonates.…”

Structure and dynamics of Penetratin’s association and translocation to a lipid bilayer

“…3 Small cationic peptides of this kind are important not only because they can penetrate cells but, additionally, some of them have been shown to possess antibiotic, 4 and/or antimicrobial properties. 5,6 The intriguing question since this discovery is: how can this highly cationic peptide (+7 charge) overcome the energetic barrier necessary to translocate into the lipid bilayer? Moreover, once inserted, how do the lipids in the membrane accommodate in presence of the strong electrostatic field generated by these charges?…”

Defensins: A Novel Approach to Use Plant Antimicrobial Peptides as an Alternative to Antibiotics

“…[20] Nevertheless, plant defensins with five disulfide bonds have been described, such as the peptide from Petunia hybrida (PhD1), whose cysteine residues interact in the following order: Cys1-Cys10, Cys2-Cys5, Cys3-Cys7, Cys4-Cys8 and Cys6-Cys9. [21] The additional disulfide bond does not affect the typical threedimensional structure of the defensin, which is located after the α-helix and the first β-sheet.…”