Professor Bernard Golding
Senior Research Investigator

  • Email: bernard.golding@ncl.ac.uk
  • Telephone: +44 (0) 191 208 6647
  • Fax: +44 (0) 191 208 6929
  • Address: Room 3.44 Bedson Building
    School of Chemistry
    Newcastle University
    Newcastle upon Tyne
    NE1 7RU, UK

 

Overview

Besides teaching 50 undergraduate and postgraduate lectures per year (see the Teaching section), my main activities are spread across two research groups (radical enzymes and anticancer drug discovery) and a spin-out company (NewChem, located in the School of Chemistry) for which I am scientific director. I currently supervise or co-supervise over 25 personnel in the School of Chemistry, a number that includes postdoctoral chemists in NewChem. Please go to the Research section for details of ongoing projects.

2012 is a major milestone in my research career as my 100th PhD student will graduate.

Qualifications

BSc and PhD (University of Manchester)

Research Publications

Total Number of Publications: > 380 which includes > 300 research papers, 31 reviews and 4 edited books (but excludes published abstracts).

Total Number of Patents: 43 listed in espacenet.com (27 in the period 2008-2012 inclusive) mainly for drug development projects (treatment of cancer, essential thrombocythemia, Alzheimer’s disease, severe pain, gastrointestinal disturbances).

Recent Awards

Honorary DPhil (2005, University of Stockholm, awarded alongside J Saramago, the 1998 Nobel Prize winner for literature).

Co-winner of First Translational Research Prize (2010, Cancer Research UK) 

Extramural Interests

Walking and cycling; improving animal welfare; cinema

 

 

 

 

Overview

Although I was trained as a synthetic organic chemist, working under Professor A Eschenmoser on the total synthesis of vitamin B12, my main interests today are the application of synthesis to the solution of problems in biology and medicine. This can mean the synthesis of isotopically labelled substrates for studying an enzyme mechanism or the synthesis of potential drugs for treating cancer. Synthesis is therefore central to all our studies and I am always looking for new ways to expedite reactions and improve methodology. Mechanistic studies are also a major focus, especially the catalytic reactions of radical enzymes. I collaborate widely in order to maximise our ability to solve interdisciplinary problems. At Newcastle, besides my separate research group studying radical enzymes, I work within a team of scientists developing new drugs against cancer targets. In 2010, we were awarded the first translational research prize from Cancer Research UK for our pioneering work on inhibitors of the DNA repair enzyme poly(ADP-ribose)polymerase. I also have a number of international collaborations, currently involving scientists in Germany, Italy, Sweden and Switzerland. My co-workers often spend time in collaborator’s laboratories and there are frequently visitors from abroad. My group is multinational with students or postdocs from China, France, Germany, India, Iran, Italy, Poland and Spain, as well as the UK. I have supervised/co-supervised nearly 100 research students, all of whom obtained the PhD degree. My research is funded by a variety of sources including the European Commission, German Research Foundation (DFG), UK Research Councils, Cancer Research UK and the pharmaceutical industry.

In addition to my academic research, I am co-director of the spin-out company NewChem, which is housed in laboratories in the School of Chemistry. This research-based operation with 18 employees works in collaboration with pharmaceutical partners to develop new therapeutic agents.

 

RESEARCH AREAS

 

Enzyme Mechanisms
Radical enzymes: anaerobic hydrocarbon 'oxidation'; coenzyme B12 – conductor or spectator?

Collaborations

M Boll (Freiburg), W Buckel (Marburg), C Chatgilaloglu (Bologna), T Darbre (Bern), R Rabus (Oldenburg), H Wilkes (Potsdam)


Selected Recent Publications

Jarling, R, Golding BT et al, ‘Stereochemical investigations reveal the mechanism of the bacterial activation of n-alkanes without oxygen’, Angew Chem Int Ed, 2012, in press (published online: 30 NOV 2011, DOI: 10.1002/anie.201106055).

Jiang D, Barata-Vallejo S, Golding BT, Ferreri C, Chatgilaloglu C, ‘Revisiting the reaction of hydroxyl radicals with vicinal  diols in water’, Org Biomol Chem, 2012, 10, 1102-1107.

Buckel W, Golding BT, ‘Radical Enzymes’ In Handbook of Radicals in Chemistry & Biology, ed by C Chatgilialoglu and A Studer, Wiley, 2012.

Friedrich P, Darley D, Golding BT, Buckel W, ‘The complete stereochemistry of the enzymatic dehydration of 4-hydroxybutyryl coenzyme A to crotonyl coenzyme A’, Angew Chem Int Ed, 2008, 47, 3254-3257.

Pierik AJ, Graf T, Pemberton L, Golding BT, Retey J, ‘But-3-ene-1,2-diol: A mechanism-based active site inhibitor for coenzyme B12-dependent glycerol dehydratase’, ChemBiochem, 2008, 9, 2268-2275.

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Anticancer Drug Design
Rational design of new anticancer agents based on the molecular pathology of cancer; current targets include DNA-dependent protein kinase, cyclin dependent kinases, MDM2-p53.

Selected Recent Publications

Saravanan K, Golding BT, Griffin RJ et al,  Nucleoside transport inhibitors: structure-activity relationships for pyrimido[5,4-d]pyrimidine derivatives that potentiate Pemetrexed cytotoxicity in the presence of alpha(1)-acid glycoprotein, J Med Chem, 2011, 54, 1847-1859.

Hardcastle IR, Golding BT et al, Isoindolinone inhibitors of the murine double minute 2 (MDM2)-p53 protein-protein interaction: structure-activity studies leading to improved potency, J Med Chem, 2011, 54, 1233-1243.

Wong C, Griffin RJ, Golding BT et al, Synthesis of sulfonamide-based kinase inhibitors from sulfonates by exploiting the abrogated SN2 reactivity of 2,2,2-trifluoroethoxysulfonates, Org Biomol Chem, 2010, 8, 2457-2464.

Cano C, Golding BT, Griffin RJ et al, Atropisomeric 8-arylchromen-4-ones exhibit enantioselective inhibition of the DNA-dependent protein kinase (DNA-PK), Org Biomol Chem, 2010, 8, 1922-1928.

Marchetti F, Golding BT, Hardcastle IR et al, Synthesis and biological evaluation of 5-substituted O4-alkylpyrimidines as CDK2 inhibitors, Org Biomol Chem, 2010, 8, 2397-2407.

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Mechanistic Toxicology

Molecular mechanisms in carcinogenesis, especially the nature of the reactive metabolites from benzene, butadiene, isoprene and chloroprene; new analytical methods to detect and quantify toxins.

Collaborations

S Rappaport and Swenberg JA (Chapel Hill), M Tornqvist (Stockholm).

Selected Recent Publications

Begemann P, Golding BT, Swenberg, JA et al, Identification and characterization of 2 '-deoxyadenosine adducts formed by isoprene monoepoxides in vitro, Chem Res Toxicol, 2011, 24, 1048-1061.

Golding BT, Barnes ML, Sadeghi MM et al, Modeling the formation and reactions of benzene metabolites, Chem-Biol Interact, 2010, 184, 196-200.

Motwani HV, Fred C, Haglund J, Golding BT, Tornqvist M, Cob(I)alamin for trapping butadiene epoxides in metabolism with Rat S9 and for determining associated kinetic parameters, Chem Res Toxicol, 2009, 22, 1509-1516.

Munter T, Golding BT, Watson WP et al, The metabolism and molecular toxicology of chloroprene, Chem-Biol Interact, 2007, 166, 323-331.

Henderson AP, Rappaport SM, Golding BT et al, Reactions of benzene oxide with thiols including glutathione, Chem Res Toxicol, 2005, 18, 265-270.

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Synthetic Methodology

New methods (e.g. SNAr reactions); novel protecting group strategies

Selected Recent Publications

Rodriguez-Aristegui S, Golding BT et al, Versatile synthesis of functionalised dibenzothiophenes via Suzuki coupling and microwave-assisted ring closure, Org Biomol Chem, 2011, 9, 6066-6074.

Suarez D, Golding BT et al, Benzylic brominations with N-bromosuccinimide in (trifluoromethyl)benzene, Synthesis, 2009, 1807-1810.

Butler P, Golding BT, Sadeghi MM et al, Fluorination and chlorination of nitroalkyl groups, Tetrahedron, 2007, 63, 11160-11166.

Seeberger S, Griffin RJ, Hardcastle IR, Golding BT, A new strategy for the synthesis of taurine derivatives using the 'safety-catch' principle for the protection of sulfonic acids, Org Biomol Chem, 2007, 7, 132-138.

Griffin RJ, Henderson A, Golding BT et al, Searching for cyclin-dependent kinase inhibitors using a new variant of the Cope elimination, J Am Chem Soc, 2006, 128, 6012-6013.

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Overview

I give ca. 50 undergraduate lectures per year in 5 courses (see below), supported by seminars and tutorials. Excellence of teaching has been validated by peer review reports and numerous student assessments, which are mostly very positive. All courses are supported by detailed high quality handouts. The lectures are continuously updated and both the handouts and Powerpoint slides are available on Blackboard. I am a co-holder with colleagues of a grant from the University’s Innovation Fund to introduce Student Response Devices (‘zappers’) as a teaching aid.

Numerous original experiments in the organic and medicinal chemistry courses have been devised by me. I recently revamped the MSc Drug Chemistry practical course to make it more relevant to the subject, with special attention to the needs of overseas students. I have also devised demonstration experiments for School Open Days and for the University's Summer 'Partners' Course.

Specific Lecture Courses

CHY2401 Structural Chemistry - Mass Spectrometry

CHY2102 Bioactive Natural Products

CHY3109 and CHY8822 Chemical Toxicology and Drug Metabolism

CHY3007 Chemical Biology

ACE2050 Introduction to Medicinal Plants