Development of bioactive peptides from the parasitic hookworm as potential treatments for autoimmune diseases

Abstract

Hookworms are parasitic nematodes that reside in the intestines of their host, where they feed on host blood. The large number of infected individuals and the long survival time inside the host makes it interesting to study the immunomodulatory activities of the hookworms. The excretory/secretory (ES) products are suspected to be responsible for these effects. One aim of this project was to fractionate the low molecular weight part (< 10 kDa) of ES products from the dog hookworm Ancylostoma caninum and test their activity in a mouse colitis model that resembles human Crohn’s disease. The results were inconclusive, but trends could be seen and it seems that two fractions might show activity in the future if the tests are scaled up. The second aim was to use Fmoc-SPPS to synthesise two disulfide-rich peptides that were identified in the transcriptome of hookworms. These peptides possess the cysteine framework of the sea anemone toxin ShK, which is able to block voltage-gated potassium channels. One peptide, Name2, was synthesised successfully and as predicted folded into a ShK-like domain as confirmed by NMR spectroscopy. The three dimensional structure of the peptide was determined and it was revealed to contain two helical segments that were braced by the three disulfide bonds. Difficulties were encountered in the synthesis of Acan1 and the correct peptide was not obtained.