A theoretical analysis of secondary structural characteristics of anticancer peptides

Abstract

Here, cluster analysis showed that a database of 158 anticancer peptides formed 21 clusters based on net positive charge, hydrophobicity and amphiphilicity. In general, these clusters showed similar median toxicities (P = 0.176) against eukaryotic cell lines and no single combination of these properties was found optimal for efficacy. The database contained 14 peptides, which showed selectivity for tumour cell lines only (ACP_CT), 123 peptides with general toxicity to eukaryotic cells (ACP_GT) and 21 inactive peptides (ACP_I). Hydrophobic arc size analysis showed that there was no significant difference across the datasets although peptides with wide hydrophobic arcs (>270°) appeared to be associated with decreased toxicity. Extended hydrophobic moment plot analysis predicted that over 50% of ACP_CT and ACP_GT peptides would be surface active, which led to the suggestion that amphiphilicity is a key driver of the membrane interactions for these peptides but probably plays a role in their efficacy rather than their selectivity. This analysis also predicted that only 14% of ACP_CT peptides compared to 45% of ACP_GT peptides were candidates for tilted peptide formation, which led to the suggestion that the absence of this structure may support cancer cell selectivity. However, these analyses predicted that ACP_I peptides, which possess no anticancer activity, would also form surface active and tilted α-helices, clearly showing that other factors are involved in determining the efficacy and selectivity of ACPs.