Hughes Laboratory: Drug Design

Research Overview

Current Projects

The Drug Discovery Laboratory uses chemical biology approaches to develop novel peptide compounds for use against a range of therapeutic targets. Following design of the compounds, the candidate molecules are synthesised in our laboratory and evaluated using appropriate in vitro and in vivo assays. Data from these assays is then used to hone the design process, with the goal of producing more active compounds that are specific to the drug target, thus limiting potential off-target effects.

Staff

Dr Susan Northfield, Postdoctoral Research Officer and Laboratory Manager
Ms Qingqing Lin, Honours Student

Collaborators

Professor Alastair Stewart, Department of Pharmacology and Therapeutics
Dr Simon Murray, Department of Anatomy and Neuroscience
Dr Junhua Xiao, Department of Anatomy and Neuroscience
Professor Stephen O’Leary, Otolaryngology, The University of Melbourne
Associate Professor Philip Thompson, Monash Institute of Pharmaceutical Sciences, Monash University
Professor David Craik, Institute for Molecular Bioscience, The University of Queensland
Professor John Wade, Howard Florey Institute
Associate Professor Ross Bathgate, Howard Florey Institute

Funding

NHMRC
Multiple Sclerosis Research Australia
The CASS Foundation
University of Melbourne Early Career Research Grant (Northfield)

Research Publications

  • Wang CK, Northfield SE, Huang Y-H, Ramos MC, Craik DJ. Inhibition of tau aggregation using a naturally-occurring cyclic peptide scaffold. European Journal of Medicinal Chemistry 2016;109: 342-349.
  • Northfield SE, Mountford SJ, Wielens J, Liu M, Zhang L, Herzog H, Holliday ND, Scanlon MJ, Parker MW, Chalmers DK, Thompson PE. Propargyloxyproline regio- and stereoisomers for click-conjugation of peptides: Synthesis and application in linear and cyclic peptides. Australian Journal of Chemistry 2015;68(9): 1365-1372.
  • Patil NA, Tailhades J, Hughes RA, Separovic F, Wade JD, Hossain MA. Cellular disulfide bond formation in bioactive peptides and proteins. International Journal of Molecular Sciences 2015;16: 1791-1805.
  • Wang CK*, Northfield SE*, Swedberg JE, Colless B, Chaousis S, Craik DJ. Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability. European Journal of Medicinal Chemistry 2015;97: 202-213. *Indicates co-authorship
  • Wong AW, Giuffrida L, Wood R, Peckham H, Gonsalvez D, Murray SS, Hughes RA, Xiao J. TDP6, a brain-derived neurotrophic factor-based trkB peptide mimetic, promotes oligodendrocyte myelination. Molecular and Cellular Neuroscience 2014;63: 132-140.
  • Wang CK*, Northfield SE*, Colless B, Chaousis S, Hamernig I, Lohman R-J, Nielsen D, Schroeder CI, Liras S, Price D, Fairlie D, Craik DJ. Rational design and synthesis of an orally bioavailable peptide guided by NMR amide temperature coefficients. Proceedings of the National Academy of Science 2014;111(49): 17504-17509. *Indicates co-authorship
  • Northfield SE, Wang CK, Schroeder CI, Durek T, Kan M-W, Swedberg JE, Craik DJ. Disulfide-rich macrocyclic peptides as templates in drug design. European Journal of Medicinal Chemistry 2014;77: 248-257.
  • Xiao J, Hughes RA, Lim JY, Wong AW, Ivanusic JJ, Ferner AH, Kilpatrick TJ, Murray SS. A small peptide mimetic of brain-derived neurotrophic factor promotes peripheral myelination. Journal of Neurochemistry 2013;125: 386-398.
  • Bathgate RA, Zhang S, Hughes RA, Rosengren KJ, Wade JD. The structural determinants of insulin-like peptide 3 activity. Frontiers in Endocrinology 2012;3: 11.
  • Shabanpoor F, Zhang S, Hughes RA, Hossain MA, Layfield S, Ferraro T, Bathgate RAD, Separovic F, Wade JD. Design and development of analogues of dimers of insulin-like peptide 3 (INSL3) B-chain as high affinity antagonists of RXFP2. Biopolymers 2011;96: 81-87.
  • Shabanpoor F, Hughes RA, Zhang S, Bathgate RAD, Layfield S, Hossain MA, Tregear GW, Separovic F, Wade JD. Effect of helix-promoting strategies on the biological activity of novel analogues of the B-chain of INSL3. Amino Acids 2010;38: 121-131.
  • Northfield SE, Roberts KD, Mountford SJ, Hughes RA, Kaiserman D, Mangan M, Pike RN, Bird PI, Thompson PE. Synthesis of ‘Difficult’ Fluorescence Quenched Substrates of Granzyme-C. International Journal of Peptide Research and Therapeutics 2010;16(3): 159-165.

Research Projects



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity, Therapeutics & Translation



Key Contact

For further information about this research, please contact Associate Professor Tony Hughes

Department / Centre

Pharmacology and Therapeutics