Address
Department of Chemistry Chemistry Research Laboratory University of Oxford Mansfield Road Oxford, OX2 8JQUnited KingdomKeywords
Bromodomains, epigenetic readers, medicinal chemistry, lysine acetylation, protein PTMs
Models
Synthetic organic chemistry, medicinal chemistry, protein expression and purification, mutagenesis, amber stop codon replacement, biophysical techniques including ITC, DSF, CPMG and STD NMR and WaterLOGSY, ALPHAScreen, X-ray crystallography, molecular modelling.
Techniques
Synthetic organic chemistry, medicinal chemistry, protein expression and purification, mutagenesis, amber stop codon replacement, biophysical techniques including ITC, DSF, CPMG and STD NMR and WaterLOGSY, ALPHAScreen, X-ray crystallography, molecular modelling.
Collaborations outside COST
N/A
Short description of ongoing research projects
Development of ligands for human and non-human bromdomains. Development of ligands for other epigenetic reader domains.
Publications
- Sekirnik née Measures, A. R.; Hewings, D. S.; Theodoulou, N. H.; Jursins, L.; Lewendon, K. R.; Jennings, L. E.; Rooney, T. P. C.; Heightman, T. D.; Conway, S. J. Isoxazole-Derived Amino Acids Are Bromodomain-Binding Acetyl-Lysine Mimics: Incorporation Into Histone H4 Peptides and Histone H3. Angew. Chem. Int. Ed. 2016, 55, 8353–8357.
- Rooney, T. P. C.; Filippakopoulos, P.; Fedorov, O.; Picaud, S.; Cortopassi, W. A.; Hay, D. A.; Martin, S.; Tumber, A.; Rogers, C. M.; Philpott, M.; Wang, M.; Thompson, A. L.; Heightman, T. D.; Pryde, D. C.; Cook, A.; Paton, R. S.; Muller, S.; Knapp, S.; Brennan, P. E.; Conway, S. J. A Series of Potent CREBBP Bromodomain Ligands Reveals an Induced-Fit Pocket Stabilized by a Cation-π Interaction. Angew. Chem. Int. Ed. 2014, 53, 6126–6130.
- Hay, D. A.; Fedorov, O.; Martin, S.; Singleton, D. C.; Tallant, C.; Wells, C.; Picaud, S.; Philpott, M.; Monteiro, O. P.; Rogers, C. M.; Conway, S. J.; Rooney, T. P. C.; Tumber, A.; Yapp, C.; Filippakopoulos, P.; Bunnage, M. E.; Muller, S.; Knapp, S.; Schofield, C. J.; Brennan, P. E. Discovery and Optimization of Small-Molecule Ligands for the CBP/P300 Bromodomains. J. Am. Chem. Soc. 2014, 136, 9308–9319.
- Hewings, D. S.; Fedorov, O.; Filippakopoulos, P.; Martin, S.; Picaud, S.; Tumber, A.; Wells, C.; Olcina, M. M.; Freeman, K.; Gill, A.; Ritchie, A. J.; Sheppard, D. W.; Russell, A. J.; Hammond, E. M.; Knapp, S.; Brennan, P. E.; Conway, S. J. Optimization of 3,5 Dimethylisoxazole Derivatives as Potent Bromodomain Ligands. J. Med. Chem. 2013, 56, 3217–3227.
- Hewings, D. S.; Wang, M.; Philpott, M.; Fedorov, O.; Uttarkar, S.; Filippakopoulos, P.; Picaud, S.; Vuppusetty, C.; Marsden, B.; Knapp, S.; Conway, S. J.; Heightman, T. D. 3,5-Dimethylisoxazoles Act as Acetyl-Lysine- Mimetic Bromodomain Ligands. J. Med. Chem. 2011, 54, 6761–6770.
Other activities of potential interest to others
Associate Editor of the Journal of Medicinal Chemistry.
