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NHMRC Early Career Fellowship (Peter Doherty Aust. Biomed. FS): Venoms to drugs: characterizing the molecular interactions between venom peptides and ion channels with a view to rational drug design (2014-2016)

Abstract

The current approach to drug development is mainly focused on small organic molecules. Unfortunately, this approach is reaching a crisis as the number of new drug leads remains constant while the cost of producing drugs is increasing. A promising alternative to small molecule drugs is to harness the rich and diverse chemistry of venom peptides that show remarkable selectivity and potency for ion channels in the nervous system. These ion channels are crucial for numerous physiological processes and are associated with a range of diseases especially nervous system disorders, chronic pain, stroke and psychiatric illnesses. This makes these ion channels attractive drug targets and venom peptides a promising source for developing novel therapeutics. To harness the rich pharmacological diversity of venom peptides for rational drug design we must understand how these peptide achieve their remarkable potency and selectivity. Hence the overall aim of this project is to characterize the molecular interactions and binding modes between selected venom peptides and ion channels to establish structure-activity relationships for rational drug design. These aims are achieved by a multidisciplinary approach that integrates biomolecular modelling, innovative fluorescence spectroscopy and experimental validation. The main outcome of this project are i) a better understanding of the molecular interactions and binding modes that govern potency and selectivity of venom peptides, ii) structure-activity relationships for selected venom peptides and ii) molecular templates for developing novel drug leads for the treatment of a range of disease, in particular nervous systems disorders, stroke and chronic pain.

Experts

Dr Evelyne Deplazes

Affiliate of ARC COE for Innovations in Peptide and Protein Science
ARC COE for Innovations in Peptide and Protein Science
Institute for Molecular Bioscience
Senior Lecturer
School of Chemistry and Molecular Biosciences
Faculty of Science
Evelyne Deplazes
Evelyne Deplazes