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Department of Chemistry

 
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

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
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
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
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
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
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
– Science advances
(2017)
3,
e1700933
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
Multisite aggregation of p53 and implications for drug rescue
G Wang, AR Fersht
– Proc Natl Acad Sci U S A
(2017)
114,
E2634
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
– Proceedings of the National Academy of Sciences of the United States of America
(2016)
113,
e7456
2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells
MR Bauer, AC Joerger, AR Fersht
– Proc Natl Acad Sci U S A
(2016)
113,
e5271
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