SMAMPs

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. 

Another approach for imparting hydrophobicity to the SMAMP is the copolymerization with nonpolar monomers (Figure 7.5g) [63]. However, the lack of differences in activity and selectivity for bacteria with varying hydrophobic/hydroplulic monomers feed ratio suggested that the balance of hydrophobic/hydroplulic segments at the polymeric unit level was crucial for obtaining active and selective polymers rather than just the global amphiphilicity. 

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

Fig. 3 Electron micrograph of negatively stained E. coli cells. Top-. Intact cell treated with a SMAMP at a concentration below the MIC. Bottom-. Disrupted cell treated with the same SMAMP at the MIC [64]...

Fig. 4 (a) Antimicrobial and hemolytic activity of three a,(3-peptides (1-3), compared to AMP magainin. (b) Axial view of predicted conformations of helical SMAMPs. Cationic residues are in red, hydrophobic residues are in black. SMAMP 1 is facially amphiphilic as an 11-helix (left column), SMAMP 2 is facially amphiphilic as a 14-helix (right column), and SMAMP 3 is facially amphiphilic in neither [65]... 

SMAMP designed not to be facially amphiphilic, either as a 14- or 11-heUx, was more selective than its helical counterparts (Fig. 4) [65]. 

Tew and coworkers also synthesize arylurea-based oligomeric SMAMPs in a one-pot synthesis (Fig. 6a, structure 2) [80]. Compared to the arylamide polymers and oligomers, (Fig. 6a, structure 1) [79], these molecules were conformationaUy even more stable due to additional hydrogen bonding, which constituted further rotational barriers around the C-C bonds of the backbone [80]. The dimer, trimer, and tetramer were obtained, of which the trimer (with an MIC90 of 0.7 pg mL ... 

Several recent studies on SMAMP polymers have investigated molecular weight effects. Overall, there seems to be no simple correlation between antimicrobial and haemolytic activity and molecular weight the body of data is limited as only a few... 

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