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