Candidacidal activity of shortened synthetic analogs of amoebapores and NK-lysin

Natural antimicrobial peptides and synthetic analogs thereof have emerged a s compounds with potentially significant therapeutical application against human pathogens. Amoebapores are 77-residue peptides with cytolytic and ant ibacterial activity considered to act by forming ion channels in cytoplasmi c membranes of the victim cells. A functionally and structurally similar pe ptide named NK-lysin exists in mammalian lymphocytes. Several synthetic ana logs of amoebapores and NK-lysin, which are substantially reduced in size c ompared to the parent molecules, were tested for their ability to inhibit t he growth of and to kill Candida albicans. Some of the peptides displayed p otent activity against a clinical isolate as well as against defined cultur e strains. Among the most active peptides found are some shortened substitu tion analogs of amoebapore C and a cationic core region of NK-lysin. As the se peptides are also highly active against Gram-positive and Gramnegative b acteria but are of low cytotoxicity towards a human keratinocyte cell line they may provide promising templates for the design of broad-spectrum pepti de antibiotics.