Oral Presentation 12th Australian Peptide Conference 2017

Pharmacology of nature-derived neuropeptide ligands (#41)

Christian W Gruber 1 2 , Maria Giulia Di Giglio 1 , Peter Keov 2 , Markus Muttenthaler 3
  1. Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
  2. School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, Australia
  3. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

The diversity in nature has long been and still is one of the biggest resources of pharmaceutical lead compounds and many natural products often exhibit biological activity against unrelated biological targets, thus providing us with starting points for pharmacological analysis. Natural peptides of great number and diversity occur in all organisms from plants to microbes to man. Examples for such rich and yet largely untapped libraries of bioactive compounds are animal venom peptides, invertebrate peptide hormones or plant defense peptides. Our goals are to discover and characterize novel oxytocin- and vasopressin neuropeptide analogs in invertebrates, study their function, determine their pharmacological activity, and use them as probes to design peptides to develop ligands for human G protein-coupled receptors. Using an interdisciplinary approach by combining physiology, pharmacology and peptide chemistry, we are aiming to generate selective, potent and stable peptide ligands and may be useful for the treatment of a wide range of challenging, but yet untreated diseases.

  1. Koehbach J, O’Brien M, Muttenthaler M, Miazzo M, Akcan M, Elliott AG, Daly NL, Harvey PJ, Arrowsmith S, Gunasekera S, Smith TJ, Wray S, Göransson U, Dawson PE, Craik DJ, Freissmuth M, Gruber CW. Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design. Proc. Natl. Acad. Sci. USA, 2013; 110: 21183-21188.
  2. Gruber CW, Koehbach J, Muttenthaler M. Exploring bioactive peptides from natural sources for oxytocin and vasopressin drug discovery. Future Med. Chem., 2012; 4: 1791-1798.
  3. Di Giglio MG, Muttenthaler M, Harpsøe K, Liutkeviciute Z, Keov P, Eder T, Rattei T, Arrowsmith S, Wray S, Marek A, Elbert T, Alewood PF, Gloriam DE, Gruber CW. Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide. Sci Rep., 2017; 7:41002.