Hookworm infections are known to cause many severe immunopathological complications in human host.1 More recently however, there has been evidence to suggest a more harmonious host-parasite interplay, with the nematodes’ ability to beneficially alter the host immune system.1 This study reports on the synthesis of hookworm-derived peptides for the future development of a potential therapeutic treatment for autoimmune disease. Several ShK-like peptides from the Ancylostoma canium and Necator americanus hookworms were synthesised using solid phase peptide synthesis and characterised using nuclear magnetic resonance spectroscopy. Cytometric bead array, intracellular cytokine staining and functional T-cell assessment assays were used to investigate their biological effect on human peripheral blood mononuclear cells. Studies using NMR spectroscopy showed that each peptide folded into a similar structural fold as the ShK toxin and this similarity was highlighted by the determination of the three dimensional structure of two of the active peptides, Acan1 and Nak1.2 Here it is shown that two out of the seven peptides significantly increased the production of different cytokines on human peripheral blood mononuclear cells. Further biological studies demonstrated that Acan1 potentially targets a novel cell type and pathway different to that of ShK to modulate the immune response. These results suggest that Acan1 might be a potential drug lead for the treatment of autoimmune diseases.