Oral Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

Venom peptides as drugs: the long and winding road (#4)

Raymond Norton 1
  1. Biochemistry, Monash University, Melbourne, Victoria, Australia

Animal venoms are a rich source of peptides that are potent and often exquisitely selective probes of the structure and function of ion channels and receptors, and as such are of significant interest to the pharmaceutical and biotech industries as both therapeutic leads and pharmacological tools.[1] I will describe our studies on peptides from sea anemones,[2] scorpions[3] and parasitic worms[4] that are potent blockers of potassium channels. Kv1.3 potassium channels play a major role in the activation of effector memory T cells, which are involved in autoimmune diseases such as multiple sclerosis, type 1 diabetes and rheumatoid arthritis.[5] Kv1.3 blockers selectively inhibit the activation of these cells and show considerable potential as therapeutics for autoimmune diseases.[6As another example of the therapeutic potential of venom peptides, evidence is emerging of peptides from venomous cone snails that target neuroendocrine processes. The fish-hunting cone snail Conus geographus elaborates insulins as a major venom component; when injected into fish, this insulin elicits hypoglycemic shock, implying that it is used as a weapon for prey capture.[7] We have determined the structure of one of these insulins, Con-Ins G1, and modelled its interaction with the insulin receptor.[8] Con-Ins G1 has the potential to guide the development of novel rapidly-acting human insulin analogues.

  1. [1] R. S. Norton, K. G. Chandy, Neuropharmacology 2017, 127, 124. [2] S. C. Chang, R. Huq, S. Chhabra, et al., FEBS J. 2015, 282, 2247. [3] M. H. Rashid, R. Huq, M. R. Tanner, et al., Sci Rep 2014, 4, 4509. [4] S. Chhabra, S. C. Chang, H. M. Nguyen, et al., FASEB J 2014, 28, 3952.
  2. [5] K. G. Chandy, R. S. Norton, Curr. Opin. Chem. Biol. 2017, 38, 97. [6] M. R. Tanner, R. B. Tajhya, R. Huq, et al., Clin. Immunol. 2017, 180, 45. [7] H. Safavi-Hemami, J. Gajewiak, S. Karanth, et al., Proc Natl Acad Sci U S A 2015, 112, 1743. [8] J. G. Menting, J. Gajewiak, C. A. MacRaild, et al., Nat. Struct. Mol. Biol. 2016, 23, 916.