Professor Sir Alan Fersht FRS | Department of Chemistry

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Portrait of arf25

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

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

– The 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

(2018)

414,

99

(DOI: 10.1016/j.canlet.2017.09.053)

Targeting mutant p53 with PK11007: A new approach for the treatment of patients with triple-negative breast cancer?

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

– Journal of Clinical Oncology

(2017)

35,

e14099

(DOI: 10.1200/jco.2017.35.15_suppl.e14099)

Structures of closed and open conformations of dimeric human ATM

D Baretić, HK Pollard, DI Fisher, CM Johnson, B Santhanam, CM Truman, T Kouba, AR Fersht, C Phillips, RL Williams

– Sci Adv

(2017)

3,

e1700933

(DOI: 10.1126/sciadv.1700933)

Multisite aggregation of p53 and implications for drug rescue

GZ Wang, AR Fersht

– Proceedings of the National Academy of Sciences of the United States of America

(2017)

114,

E2634

(DOI: 10.1073/pnas.1700308114)

Multisite aggregation of p53 and implications for drug rescue

G Wang, AR Fersht

– Proceedings of the National Academy of Sciences

(2017)

114,

E2634

(DOI: 10.1073/pnas.1700308114)

Design of a molecular support for cryo-EM structure determination.

TG Martin, TAM Bharat, AC Joerger, X-C Bai, F Praetorius, AR Fersht, H Dietz, SHW Scheres

– Proc Natl Acad Sci U S A

(2016)

113,

E7456

(DOI: 10.1073/pnas.1612720113)

2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells

MR Bauer, AC Joerger, AR Fersht

– Proceedings of the National Academy of Sciences

(2016)

113,

E5271

(DOI: 10.1073/pnas.1610421113)

An in silico algorithm for identifying stabilizing pockets in proteins: Test case, the Y220C mutant of the p53 tumor suppressor protein

D Bromley, MR Bauer, AR Fersht, V Daggett

– Protein engineering, design & selection : PEDS

(2016)

29,

377

(DOI: 10.1093/protein/gzw035)