Cationic peptides antibiotic activities

Gough MA, Hancock REW, Kelly NM. Anti-endotoxin activity of cationic peptide antibiotics. Infect immun 1996 64 4922-4927. 

Many plant-derived di- and tri-peptides were proved to be active against HSV and measles virus (MV). These peptides consist mainly of carbobenzoxy derivatives of phenylalanine [11]. Cationic peptides are used as nature s antibiotics, being produced in response to an infection in virtually most organisms including plants and insects. Cationic peptides and proteins are now proceeding through clinical trials as topical antibiotics and antiendotoxins [136]. 

The ability of cationic peptides to act in synergy with certain classical antibiotics (68) can be explained by their ability to disrupt outer membrane integrity, promoting the uptake of antibiotics across this barrier. Interestingly, the most potent cationic peptides do not have this enhancer activity for most antibiotics, presumably since they kill cells... 

Cationic peptides do not have as potent activities against the most susceptible bacteria as do Other antibiotics. Furthermore, the spectrum of cationic peptides includes some of the most potent toxins (e.g., bee venom and scorpion toxin), so that toxicity will always be a closely observed issue. In addition, being peptides, they are potentially susceptible to host... 

Cationic amphipathic CPs, whose nanotubes are oriented parallel to the membrane, have been found to have quite potent and selective antibiotic activity both in vitro and in vivo. The proposed mode of action for this type of peptide is based on a carpet-like mechanism, in which several nanotnbes lie parallel to the membrane surface. Antiviral activity has also been found for this type of CP and the mechanism of action proposed is based on interference of the virus fusion with the cell membrane. Interestingly, mannopeptimycins are very potent antimicrobial agents obtained from natural sources and these contain a hexacyclicpeptide that can be considered as a d,l-o -CP. The mechanism of action for these systems is not known yet, but could be based on the formation of amphipathic nanotnbes. Very recently, D,L-a-glycopeptide analogs have been designed and prepared for their potential applications as antimicrobial agents. ... 

The interaction between cyclic peptides and metal cations is closely related to their activities as antibiotics and to ion transport processes. An example of such interaction by a cyclic dipeptide is the complex formed by Li and cyc/o(Sar)2. The Li forms four Li" —O ligands (the length of which is near 1.92 A) with the C=0 groups of four independent cyc/o(Sar)2 molecules that surround the Li" in a tetrahedral array. The other C=0 of each dipeptide coordinates to another Li" to make an infinite two-dimensional network in the crystal (Takahashi et a/., 1977). 

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