Invited Plenary 11th Asia-Pacific Congress of the International Society on Toxinology 2021

Its a fine line between pleasure and pain (#57)

David J Craik 1
  1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

Our work focuses on the discovery of cyclic peptides from plants and animals and their applications in drug design and agriculture. We have a particular interest in a family of mini-proteins called cyclotides, which comprise ~30 amino acids and incorporate three disulfide bonds arranged in a cystine knot topology, which makes them exceptionally stable. Cyclotides occur in all plants from the Violaceae family and in certain plants from the Rubiaceae, Cucurbitaceae, Solanaceae and Fabaceae, where they are present as host defense agents against insects and nematodes. To illustrate the diversity of cyclotide applications I will describe one recent novel application of a cyclotide from the plant Hybanthus enneaspermus as a libido-enhancing agent (1). We also study disulfide rich peptides from cone snail venoms as potential leads for pain treatments (2). I will describe how structures of these classes of molecules show that there is a fine line between pleasure and pain.

  1. Du Q, Huang Y-H, Bajpai A, Frøsig-Jorgensen M, Zhao G, Craik D J: Evaluation of the in vivo aphrodisiac activity of a cyclotide extract from Hybanthus enneaspermus. Journal of Natural Products (2020) 83, 3736-3743.
  2. Poth A G, Chiu F C K, Stalmans S, Hamilton B R, Huang Y-H, Shackleford D M, Patil R, Le T T, Kan M-W, Durek T, Wynendaele E, De Spiegeleer B, Powell A K, Venter D J, Clark R J, Charman S A, Craik D J: Effects of backbone cyclisation on the pharmacokinetics and drug efficiency of the orally active analgesic conotoxin cVc1.1. Medicine in Drug Discovery (2021) 10, 100087.