Centre for Synthetic Biology and the Bioeconomy

Staff Profile

Emeritus Professor Bernard Golding

Emeritus Professor

Background

Overview

My main research activities are spread across two areas (drug discovery and radical enzymes ) and two spin-out companies (NewChem Technologies and BiBerChem Research, based in the Biosphere on the Newcastle Helix site) for which I am scientific director.

I am a co-inventor of the drug rucaparib (Rubraca), approved by the FDA and EMA for treatment of BRCA-mutant ovarian cancer and available via the NHS.

I have supervised/co-supervised 100 PhD students successfully to graduation, as well as the research projects of ca. 100 master's/ERASMUS students.

Qualifications

BSc and PhD (University of Manchester); honorary DPhil (University of Stockholm).

Research Publications

Total Number of Publications: 468 including 348 research papers, 40 reviews, 10 commentaries and 4 edited books (164 research papers and 15 reviews since 2000) [data from Web of Science]. Note: published abstracts are excluded.

Total Number of Patents: 60 listed in espacenet.com mainly for drug development projects (cancer treatment, essential thrombocythemia, Alzheimer’s disease, severe pain, gastrointestinal disturbances).

Recent Awards

2019 Robert Robinson Award of the Royal Society of Chemistry, for contributions to biochemistry, microbiology and medicine.

2010 Co-winner of the 1st Cancer Research UK ‘Translational Research Prize’, for inventing and developing potent inhibitors of polyADP-ribose polymerase-1 leading to the drug rucaparib/Rubraca.

2005 Doctor of Philosophy cum lauda (University of Stockholm, 2005) [awarded alongside J Saramago, winner of Nobel Prize for Literature 1998].

Extramural Interests

Walking/running (raising money for charities); cycling; improving animal welfare; cinema (especially Coen brothers).

 

 

 

Research

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 my 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 the ability to solve interdisciplinary problems. At Newcastle, besides my research studying radical enzymes, I have worked within a team of scientists developing new drugs against cancer targets. I was co-founder of this group in 1990 (with A H Calvert and D R Newell). 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 had many international collaborations, involving scientists in Australia, Germany, Italy, Japan, Sweden and Switzerland. My co-workers have often spent time in collaborator’s laboratories and there have been frequent visitors from abroad. My group has always been multinational with students or postdocs from e.g. China, France, Germany, India, Iran, Italy, Poland and Spain, as well as the UK. I have supervised/co-supervised more than 100 research students, all of whom obtained the PhD degree. My research has been 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 scientific director of the spin-out companies NewChem Technologies (founded 2002) and BiBerChem Research (2017), which are housed in the Biosphere, Newcastle Helix site. NewChem has 23 employees currently, many of whom are former Newcastle chemistry graduates, and works in collaboration with pharmaceutical and academic partners to develop new therapeutic agents.

 

RESEARCH AREAS


 Application of chemical synthesis and mechanistic studies to the solution of problems in biology and medicine: 

Drug Discovery.- rational design of new anticancer agents based on the molecular pathology of cancer; targets include poly(ADP-ribose) polymerases, DNA-dependent protein kinase, cyclin dependent kinases and the MDM2/p53 protein-protein interaction [collaboration with colleagues in Chemistry [R J Griffin (deceased), M J Waring et al] and Newcastle Medical School (A H Calvert, D R Newell et al)]. Interdisciplinary research at Newcastle University discovered the first potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1) through medicinal chemistry (directed by myself and R J Griffin), cancer pharmacology and preclinical work leading to first-in-human clinical studies. This research led to the development of the drug rucaparib (trade name Rubraca), which was granted approval by the US Food & Drug Administration (2016) and European Medicines Agency (2018) for the treatment of BRCA mutant ovarian cancer and is now available via the NHS.

The importance of the Newcastle team’s contribution was recognised by the award (2010) of the first Cancer Research UK Translational Cancer Research prize to Golding and Griffin (School of Chemistry) with A H Calvert, N J Curtin, B Durkacz, D R Newell (Northern Institute for Cancer Research). This research was also the basis of School of Chemistry Impact Cases for the 2014 and 2021 Research Excellence Framework (REF) achieving a 4* rating in both.

Enzyme Mechanisms.- especially unusual or ‘impossible’ reactions including those for which radicals are intermediates, e.g. coenzyme B12-dependent reactions; anaerobic functionalisation of hydrocarbons and prebiotic enzyme-like processes [partly in collaboration with: W Buckel, H Heider (Marburg); R Rabus, H Wilkes (Oldenburg); C Chatgiliagolu (Bologna)].

Synthetic Organic Chemistry.- synthesis of biologically active molecules including specifically labelled compounds; development of new methodology including protecting groups; use of 2,2,2-trifluoroethanol in synthesis; bifurcating hydrogen bonding for catalysing epoxide reactions with amine nucleophiles.

Other Research.- Molecular toxicology (atmospheric pollutants, e.g. benzene), prebiotic chemistry, hydrogen production (clean energy), carbon dioxide sequestration; environmental chemistry.

 

Publications

Total Number of Publications: 468 including 348 research papers, 60 patents, 40 reviews, 10 commentaries and 4 edited books (164 research papers, 57 patents, and 15 reviews since 2000) [Web of Science and espacenet.com data excluding published abstracts].


10 Highly Cited Publications since 2000

1.     White AW, Griffin RJ, Golding BT et al, Synthesis and biological properties of benzimidazole inhibitors of the DNA repair enzyme poly(ADP-ribose)polymerase (PARP), J Med Chem, 2000, 43, 4084-4097 [264 citations]

2.     Arris CE, Golding BT, Griffin RJ et al, Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles, J Med Chem, 2000, 43, 2797-2804 [200 citations]

3.     Smith DM, Golding BT, Radom L, Understanding the mechanism of B12-dependent diol dehydratase: A synergistic retro-push-pull proposal, J Am Chem Soc, 2001, 123, 1664-1675 [90 citations]

4.     Davies TG, Golding BT, Griffin RJ et al, Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor, Nat Chem Biol, 2002, 9, 745-749 [196 citations]

5.     Leahy JJJ, Golding BT, Griffin RJ et al, Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries, Bioorg Med Chem Lett, 2004, 14, 6083-6087 [307 citations]

6.     Buckel W, Golding BT, Radical enzymes in anaerobes. Annu Rev Microbiol. 2006, 60, 27-49 [139 citations]

7.     Wang X, Golding BT, Scott, K et al, A polytetrafluoroethylene-quaternary 1,4-diazabicyclo-[2.2.2]-octane polysulfone composite membrane for alkaline anion exchange membrane fuel cells, Int J Hydrogen Energy, 2011, 36, 10022-10026 [71 citations]

8.     Hardcastle IR, Golding BT, Griffin RJ 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[125 citations]

9.     Jarling R, Golding BT, Wilkes H et al, Stereochemical investigations reveal the mechanism of the bacterial activation of n-alkanes without oxygen, Angew Chem Intl Edn, 2012, 51, 1334-1338 [53 citations]

10.  Kimes NE, Callaghan AV, Golding BT et al, Metagenomic analysis and metabolite profiling of deep-sea sediments from the Gulf of Mexico following the Deepwater Horizon oil spill, Frontiers Microbiol, 2013, 4, Article no 50 [187 citations]



--------------------------------------------------------------------------------

 

Teaching

 

Overview

I have delivered around 2000 lectures during my academic career covering most areas of orgnaic chemistry (including biological, medicinal and synthetic chemistry).

Recent Courses

Structural Chemistry - Mass Spectrometry

Bioactive Natural Products

Chemical Toxicology and Drug Metabolism

Chemical Biology

 

 

 


Publications