Oral Presentation 11th Australian Peptide Conference 2015

Minituarised alpha-conotoxins that target the GABA(B) receptor. (#60)

Richard J Clark 1 , Bodil B Carstens 2 , Geza Berecki 3 , Kathryn Jackson 4 , James Daniel 4 , David J Adams 3 , David J Craik 2
  1. University of Queensland, Brisbane, QLD, Australia
  2. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
  3. Innovations Research Institute, RMIT University, Melbourne, Victoria, Australia
  4. School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia

Conotoxins are peptide toxins, ranging in size from 12 to 30 amino acids, isolated from the venom of snails from the Conus genus [1]. A subfamily of conotoxins, the alpha-conotoxins, were believed to interact only with nicotinic acetylcholine receptors (nAChRs), which have been implicated in a range of disorders, including Alzheimers disease, schizophrenia, depression and small cell lung carcinoma and also play a role in analgesia and addiction [2]. However, recently we showed that a subset of the alpha-conotoxins also modulate N-type calcium channels by acting as agonists of the G-protein-coupled GABAB receptor [3]. GABAB receptors [4] are G-protein coupled receptors for g-aminobutyric acid (GABA), the main inhibitory neurotransmitter of the brain, and are a promising target for the treatment of a range of neurological and psychiatric disorders including pain, depression and drug addiction [5]. One member of this conotoxin subset, Vc1.1, has now been developed as an orally active lead molecule for the treatment of neuropathic pain [6]. This presentation will describe our recent discovery of miniaturised versions of these alpha-conotoxins target that retain their ability to target the GABAB receptor and represent potential new drug leads for treating neuropathic pain.

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  5. Brauner-Osborne H, Wellendorph P, & Jensen AA (2007) Curr Drug Targets 8(1):169-184.
  6. Clark RJ, et al. (2010) Angew Chem Int Ed Engl 49(37):6545-6548.