The effect of the length and flexibility of the side chain of basic amino acids on the binding of antimicrobial peptides to zwitterionic and anionic membrane model systems

Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted Cα amino acids

“…45,60,61 The determining factor for whether the basic amino acid substitution has an effect on the antibacterial activity seems to be the chemical composition of the bacterial cell membrane(s). For example the cell membrane of drug resistant S. aureus contains as much as 38% of the cationic phospholipid lysylphosphatidylglycerol which is known to repel antimicrobial peptides.…”

“…[12][13][14] Previous CD investigations using the Tic-Oic series of AMPs has shown modifications of the primary sequence of the AMP by incorporating various unnatural amino acids will affect the final membrane bound conformation and thus antibacterial activity of the AMP. 45,55,56 Due to the high percentage of unnatural amino acids incorporated into the primary sequence of the Tic-Oic and the A6c/A5c series of AMPs deconvolution programs to predict percentages of secondary structure can not be employed. 43 …”

“…45,55,56 Because the interactions that occur between an AMP and a lipid membrane are so complex and coupled with the fact that small modifications in the sequence of an AMP can dramatically alter membrane binding, quantitative correlations between specific amino acids and activity are not currently possible. Therefore for the purposes of our discussions only qualitative comparisons will be discussed.…”

“…9,44,45,73 HPLC retention time data has been employed in the literature to correlate AMP hydrophobicity with antibacterial activity. 74 In this method of analysis an increase in the retention time of one AMP compared to another implies an increase in hydrophobicity of said AMP in aqueous environments.…”

Spectral and biological evaluation of a synthetic antimicrobial peptide derived from 1-aminocyclohexane carboxylic acid

“…9,[34][35][36][37]42,43 The structure and physicochemical properties of these AMPs were defined by incorporating several Tic-Oic dipeptide units and other unnatural amino acids into the primary amino acid sequence. The AMPs designed using this protocol exhibited below 25 lM to above 400 nM in vitro inhibitory activity against a variety of bacterial strains including drug resistant strains as well as select agents.…”