Synthesis and biological activity of lipophilic analogs of the cationic antimicrobial active peptide anoplin

In this study, novel analogs of anoplin were prepared and examined for their antimicrobial, hemolytic activity, and proteolytic stability. Specific substitutions were introduced in amino acids Gly1, Arg5, and Thr8 and lipophilic groups with different lengths in the N‐terminus in order to investigate how these modifications affect their antimicrobial activity. These cationic analogs exhibited higher antimicrobial activity than the native peptide; they are also nontoxic at their minimum inhibitory concentration (MIC) values and resistant to enzymatic degradation. The substituted peptide GLLKF5IKK8LL‐NH2 exhibited high activity against Gram‐negative bacterium Zymomonas mobilis (MIC = 7 µg/ml), and the insertion of octanoic, decanoic, and dodecanoic acid residues in its N‐terminus increased the antimicrobial activity against Gram‐positive and Gram‐negative bacteria (MIC = 5 µg/ml). The conformational characteristics of the peptide analogs were studied by circular dichroism. Structure activity studies revealed that the substitution of specific amino acids and the incorporation of lipophilic groups enhanced the amphipathic α‐helical conformation inducing better antimicrobial effects. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Selected substitutions of the residues Gly1 → Lys, Gly1 → Arg, Arg5 → Phe, and Thr8 → Lys in the natural cationic antimicrobial peptide anoplin Gly1‐Leu2‐Leu3‐Lys4‐Ar...

Source: Journal of Peptide Science - November 14, 2016 Category: Biochemistry Authors: Kostas Chionis, Dimitrios Krikorian, Anna ‐Irini Koukkou, Maria Sakarellos‐Daitsiotis, Eugenia Panou‐Pomonis Tags: Research Article Source Type: research