Professor Sir Alan Fersht FRS

Our major research programme concerns the folding, stability and activity of proteins. We apply a broad multi-disciplinary approach that combines methods and ideas of molecular biology and physical-organic chemistry. We use techniques including protein engineering, DNA cloning, sequencing and mutagenesis, cell culture, gene and peptide synthesis, spectroscopy, rapid reaction techniques, multi-dimensional NMR (we have a 500, 600, 700 and an 800 MHz spectrometers) and x-ray protein crystallography.

Current major projects include: protein folding, misfolding and disease; drug discovery; and structure-activity relationships of proteins involved in cancer and disease.

Although now emeritus, I am still fully active in research with long term funding, including an MRC Programme Grant.

Publications

Targeting Cavity-Creating p53 Cancer Mutations with Small-Molecule Stabilizers: The Y220X Paradigm

MR Bauer, A Krämer, G Settanni, RN Jones, X Ni, R Khan Tareque, AR Fersht, J Spencer, AC Joerger

– ACS chemical biology

(2020)

15,

657

(DOI: 10.1021/acschembio.9b00748)

ChemBioChem@20-Some Reflections

AR Fersht, P Gölitz, J-M Lehn

– Chembiochem

(2019)

21,

(DOI: 10.1002/cbic.201900658)

SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promising Activity in Hepatocellular Carcinoma.

S Gomes, B Bosco, JB Loureiro, H Ramos, L Raimundo, J Soares, N Nazareth, V Barcherini, L Domingues, C Oliveira, A Bisio, S Piazza, MR Bauer, JP Brás, MI Almeida, C Gomes, F Reis, AR Fersht, A Inga, MMM Santos, L Saraiva

– Cancers (Basel)

(2019)

11,

1151

(DOI: 10.3390/cancers11081151)

A structure-guided molecular chaperone approach for restoring the transcriptional activity of the p53 cancer mutant Y220C.

MR Bauer, RN Jones, RK Tareque, B Springett, FA Dingler, L Verduci, KJ Patel, AR Fersht, AC Joerger, J Spencer

– Future medicinal chemistry

(2019)

11,

2491

(DOI: 10.4155/fmc-2019-0181)

Aminobenzothiazole derivatives stabilize the thermolabile p53 cancer mutant Y220C and show anticancer activity in p53-Y220C cell lines.

MGJ Baud, MR Bauer, L Verduci, FA Dingler, KJ Patel, D Horil Roy, AC Joerger, AR Fersht

– Eur J Med Chem

(2018)

152,

101

(DOI: 10.1016/j.ejmech.2018.04.035)

Mutant p53 as a therapeutic target for the treatment of triple-negative breast cancer: Preclinical investigation with the anti-p53 drug, PK11007.

NC Synnott, MR Bauer, S Madden, A Murray, R Klinger, N O'Donovan, D O'Connor, WM Gallagher, J Crown, AR Fersht, MJ Duffy

– Cancer Letters

(2018)

414,

(DOI: 10.1016/j.canlet.2017.09.053)

The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53.

E Madan, TM Parker, MR Bauer, A Dhiman, CJ Pelham, M Nagane, ML Kuppusamy, M Holmes, TR Holmes, K Shaik, K Shee, S Kiparoidze, SD Smith, Y-SA Park, JJ Gomm, LJ Jones, AR Tomás, AC Cunha, K Selvendiran, LA Hansen, AR Fersht, K Hideg, R Gogna, P Kuppusamy

– The Journal of biological chemistry

(2018)

293,

4262

(DOI: 10.1074/jbc.RA117.000950)