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Antimicrobial peptides (AMPs) are interesting compounds owing to their ability to kill several pathogens. In order to identify new AMPs, c-PLAI analogues were synthesized and evaluated together with their linear precursors for their antimicrobial properties against two Gram-positive bacteria ( Staphylococcus aureus  and  Bacillus cereus ), two Gram-negative bacteria ( Escherichia coli  and  Klebsiella pneumoniae ), and two fungal strains ( Candida albicans  and  Trichophyton mentagrophytes ). The new c-PLAI analogues were prepared through a combination of solid- and solution-phase syntheses, as previously employed for the synthesis of c-PLAI. The antimicrobial activity tests showed that the synthetic parent peptide c-PLAI was inactive or weakly active towards the bioindicators employed in the assay. The tests also indicated that cyclic c-PLAI analogues possessed enhanced antimicrobial properties against most of the bacteria and fungi tested. Furthermore, this study revealed that analogues containing cationic lysine residues displayed the highest activity towards most bioindicators. A combination of lysine and aromatic residues yielded analogues with broad-spectrum antimicrobial properties.

Synthesis of cyclotetrapeptide analogues of c-PLAI and evaluation of their antimicrobial properties