Poster Presentation 13th Australian Peptide Conference 2019

Applications of cyclotides in the pharmaceutical and agricultural industries (#162)

Meng-Wei Kan 1 , David J. Craik 1
  1. The University of Queensland, Brisbane, QLD, Australia

Naturally-occurring peptides offer great potential as leads for drug design but often suffer from a number of disadvantages, which hinder their translation from bench to clinic. Cyclotides are bioactive peptides from plants that have exceptional stability owing to their cyclic peptide backbone and knotted arrangement of three conserved disulfide bonds. They are amongst nature’s most stable proteins which makes them excellent templates for drug design applications. Recent applications of cyclotides and related peptides include the design of drugs for cancer,1 pain2 and thrombosis.3 The application of cyclotides also extend to the agricultural industry due to their high target selectivity as well as lower toxicity compared to traditional chemical pesticides. A cyclotide-containing product (Sero-X) reached the market as a commercial bio-friendly insecticide in 2017. The applications of cyclotides have been extensively reviewed. This presentation provides an analysis of trends in cyclotide literature over the last three decades and aims to be a useful resource for following the development of the cyclotide field and for introducing new researchers to the complete literature of the field.4

 

  1. Huang, Y.-H.; Henriques, S. T.; Wang, C. K.; Thorstholm, L.; Daly, N. L.; Kaas, Q.; Craik, D. J. Design of substrate-based BCR-ABL kinase inhibitors using the cyclotide scaffold. Sci. Rep. 2015, 5, 12974.
  2. Castro, J.; Grundy, L.; Deiteren, A.; Harrington, A. M.; O'Donnell, T.; Maddern, J.; Moore, J.; Garcia-Caraballo, S.; Rychkov, G. Y.; Yu, R.; Kaas, Q.; Craik, D. J.; Adams, D. J.; Brierley, S. M. Cyclic analogues of α-conotoxin Vc1.1 inhibit colonic nociceptors and provide analgesia in a mouse model of chronic abdominal pain. Br. J. Pharmacol. 2018, 175, 2384-2398.
  3. Swedberg, J. E.; Mahatmanto, T.; Abdul Ghani, H.; de Veer, S. J.; Schroeder, C. I.; Harris, J. M.; Craik, D. J. Substrate-guided design of selective FXIIa inhibitors based on the plant-derived Momordica cochinchinensis trypsin inhibitor-II (MCoTI-II) scaffold. J. Med. Chem. 2016, 59, 7287-7292.
  4. Kan, M.-W.; Craik, D. J. CHAPTER 14 Trends in Cyclotide Research. In Cyclic Peptides: From Bioorganic Synthesis to Applications, The Royal Society of Chemistry: 2018, pp 302-339.