SHORTENED AMOEBAPORE ANALOGS WITH ENHANCED ANTIBACTERIAL AND CYTOLYTIC ACTIVITY

Amoebapores are cytolytic peptides of Entamoeba histolytica which func tion by the formation of ion channels in target cell membranes. Three isoforms (amoebapore A, B, and C) exist in amoebic cytoplasmic granule s. They are composed of 77 amino acid residues arranged in four alpha- helical domains. In order to analyze the structure-function relationsh ips, 15 synthetic peptides of 24-25 residues were constructed based on the assumption that the third helix is the membrane-penetrating domai n and on the previous finding that positively charged residues are sig nificant for activity. Activity of these short versions of amoebapores was determined towards artificial and natural targets, such as liposo mes, bacteria, erythrocytes and a human tumor cell line. It was found that some of the novel peptides were highly active and showed a broade r activity spectrum compared to the parent molecules.