Synthetic mimics of antimicrobial peptides

Scott RW, DeGrado WF, Tew GN (2008) De novo designed synthetic mimics of antimicrobial peptides. Curr Opin Biotechnol 19 620-627... 

Al-Badri and co-workers [55] studied the effect of fine-tuning the cationic parameter of synthetic mimics of antimicrobial peptides (SMAMP) on haemolytic and antibacterial activities. A category of novel norbornene monomers that carry one, two or three Boc-protected amine-functionalities was synthesised (Figure 3.8). ROMP of the monomers, followed by deprotection of the amine groups led to cationic antimicrobial polynorbornenes that carry one, two and three charges per monomer repeat unit. It was observed that enhancing the number of amine groups on the most hydrophobic polymer effectively decreased its haemolytic activity. 

Figure 7.5 Amphiphilic ROMP polymers designed as synthetic mimics of antimicrobial peptides.

Antibacterial Peptidomimetics Polymeric Synthetic Mimics of Antimicrobial Peptides... 

Keywords Antibacterial polymers Antimicrobial polymers Peptide analogs Peptidomimetics Polymer-membrane interaction Synthetic mimics of antimicrobial peptides, SMAMPs... 

Tew and co-workers studied the biological activities of antimicrobial polymers and found that they were influenced by the amphiphilicity of the polymer or oligomer as an entity rather than the activity of one antimicrobial portion, either embedded or covalently attached, and mostly contained antimicrobial macromolecules that can mimic the biological action of antimicrobial natural host-defence peptides (e.g., synthetic polyphenylene ethynylenes, polynorbornenes and polymethacrylates) [4]. 

As mentioned in the introduction to this chapter, the recent discovery of thiolactone peptides as potential antimicrobial agents, based on flieir ability to act as antagonists of natural auto-inducing peptides (AIP), prompted the new synthetic achievements, which permitted the synthesis of these cyclic peptide inhibitors. Here, we discuss the most recent achievement in the synthesis of AIP mimics, based on an original linker for the Fmoc-based solid-phase methodology. 

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