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Yusuf Hamied Department of Chemistry

 

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

From covalent transition states in chemistry to noncovalent in biology: from β- to Φ-value analysis of protein folding.
AR Fersht
– Quarterly reviews of biophysics
(2024)
57,
e4
(doi: 10.1017/s0033583523000045)
NF-κB Rel subunit exchange on a physiological timescale.
M Biancalana, E Natan, MJ Lenardo, AR Fersht
– Protein Science
(2021)
30,
1818
(doi: 10.1002/pro.4134)
AlphaFold - A Personal Perspective on the Impact of Machine Learning.
AR Fersht
– Journal of molecular biology
(2021)
433,
167088
(doi: 10.1016/j.jmb.2021.167088)
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,
5
(doi: 10.1002/cbic.201900658)
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 Med Chem
(2019)
11,
2491
(doi: 10.4155/fmc-2019-0181)
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
(2019)
11,
1151
(doi: 10.3390/cancers11081151)
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
– European journal of medicinal chemistry
(2018)
152,
101
(doi: 10.1016/j.ejmech.2018.04.035)
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
– Journal of Biological Chemistry
(2018)
293,
4262
(doi: 10.1074/jbc.ra117.000950)
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 Lett
(2017)
414,
99
(doi: 10.1016/j.canlet.2017.09.053)
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