We are a team of multidisciplinary experts in Fragment-Based Design. Our research is underpinned by four research themes:

Fragment Library Design

Industry partners: VAST Bioscience, Vernalis R&D, CSIRO

Developing libraries of chemical fragments to cover chemical space and potentially uncover new and valuable bioactive molecules.

  • Cubane as a 3D scaffold for fragment library construction

Fragment Screening

Industry partners: Takeda, Vernalis R&D, Mestrelab, CSIRO

Optimising biophysical screening methods and fragment hit ranking strategies to identify compounds that bind to a target protein & accelerate lead development.

  • Develop fragment screening methods using mass spectrometry (MS), nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR)
  • Development of automated analysis of biophysical screening data (NMR, SPR and X-ray crystallography)
  • New NMR methods to characterise the ligand binding modes in protein-ligand complexes not amenable for X-ray crystallography
  • NMR dynamics in ps-s time scales for investigating the structural origins of cryptic sites on proteins
  • 3D structure determination of peptides and proteins by solution NMR spectroscopy
  • Implementation/development of new NMR methods to support fragment-/structure-based drug design

Protein Expression & Sample Preparation

Industry partners: TetraGenetics, Takeda, Vernalis R&D

Developing novel approaches to sample preparation and screening to enable FBD for larger, more complex and membrane-bound proteins.

  • Enabling fragment-based lead discovery for challenging targets, such as ion channels and G-protein coupled receptors (GPCRs)
  • Synthesis of aromatic 19F-13C TROSY-NMR probes to enable detailed study of the function and dynamics of biomolecular structures
  • Develop membrane protein preparations for use on SPR chips

Fragment Elaboration

Industry partner: Vernalis R&D

Developing and optimising systematic approaches to selecting suitable fragments for development and enhancement into potent leads.

  • Optimisation of REFiL (Rapid Elaboration of Fragments into Leads) strategy to accelerate the process of target validation
  • Novel chemoinformatic methods for fragment exploration and design
  • Microscale parallel synthesis and biophysical screening for rapid fragment development
  • Developing isoform-selective inhibitors of fatty acid-binding proteins as novel therapeutics for metabolic disorders and cancer
  • Development of inhibitors for the extra-terminal domain of bromodomain-3 (BRD3-ET) using a REFiL approach
  • Finding inhibitors of novel antivirulence targets