Prof. Beining Chen
Department of Chemistry
Professor of Medicinal Chemistry
+44 114 222 9467
Full contact details
Department of Chemistry
13 Brook Hill
After a BSc (1984) and MSc (1987) in China, Prof Chen obtained a PhD in Chemistry from the University of Glasgow in 1991. Subsequently, she became a Research Fellow at the Dyson-Perrins Laboratory in Oxford (1993-1995), after which she became a Research Fellow and then Lecturer at the University of Cranfield (1996-2002). In 2002 she became a Lecturer at the University of Sheffield, where she was promoted to Professor in 2014.
- Research interests
The major focus of our research is to use computer aided molecular design and combinatorial chemistry to facilitate drug design and molecular recognition studies.
TSEs, are progressive, invariably fatal neurological disorders occurring in sheep, cattle and humans, and in a variety of other ungulates, felines and rodents. The disease involves the formation of pathological deposits of protein in the brain. The protein responsible, the non-infectious cellular isoform of prion protein (PrPC), can adopt an aberrant insoluble infectious conformation (PrPRes), which accumulates extracellularly and is resistant to denaturation and digestion with protease. Aggregation of PrPRes leads to neural disorder and thereafter the death of animals and humans affected. The development of therapeutic compounds has always been considered as one of the most important and challenge areas to be tackled in TSE research. The project aims to develop drugs which interacts with the biosynthetic pathway of prion protein either to stabilise its conformation or to provoke the interaction of the protein with its abnormal counterpart.
Our main focus now is to develop novel drugs for prion disease to cure Transmissible Spongiform Encephalopathies (TSEs) including Scrapie in Sheep, BSE in cattles and CJD in humans. Novel ideas together with a well written proposal have recently secured her group major funding from the Department of Health worth over £1.15 million. We are also building up our research in natural product chemistry/bioorganic chemistry for lead discovery. Activities in therapeutics are expanding into other amyloid diseases as well as areas cardiovascular, CNS, anti-viruses.
Proteomics - Structural Studies of Abnormal Prion Proteins
With very few exceptions, all cells in the human body contain the same genes. We need to know what proteins are produced and are active in different cells and at different times, because it is the proteins that make things happen. For example, they govern how cells communicate with each other to mobilise an immune response, or to detect and respond to changes in their environment. The genome is a parts list and the proteome (the complement of proteins) is an activity report. Proteomics is about understanding the function of proteins, both individually and collectively.
The most challenging area in the study of TSE is to understand how abnormal prion protein forms, and its structure and functions. Modern available technologies such as x-ray crystallography and NMR prove to be little use in studying the abnormal prion conformation due to the special insoluble properties of the plaque formed during protein aggregation. Theoretical modelling using molecular dynamics and bioinformatics as tools together with various labelling techniques are being developed in Prof. Chen's group for the prediction of abnormal prion structures.
- RENATE : a pseudo-retrosynthetic tool for synthetically accessible de novo design. Molecular Informatics, 41(4).
- Corosolic acid and its structural analogs: a systematic review of their biological activities and underlying mechanism of action. Phytomedicine, 153696-153696.
- Amyloid binding and beyond: a new approach for Alzheimer's disease drug discovery targeting Aβo–PrPC binding and downstream pathways. Chemical Science. View this article in WRRO
- Glucosylpolyphenols as inhibitors of Aβ-induced Fyn kinase activation and Tau phosphorylation: synthesis, membrane permeability, and exploratory target assessment within the scope of type 2 diabetes and Alzheimer’s disease. Journal of Medicinal Chemistry. View this article in WRRO
- Enhancing reaction-based de novo design using a multi-label reaction class recommender. Journal of Computer-Aided Molecular Design. View this article in WRRO
- Application of the Cleavable Isocyanide in Efficient Approach to Pyroglutamic Acid Analogues with Potential Biological Activity. Russian Journal of General Chemistry, 89(12), 2562-2570.
- Development and application of a data-driven reaction classification model : comparison of an electronic lab notebook and the medicinal chemistry literature. Journal of Chemical Information and Modeling, 59(10), 4167-4187. View this article in WRRO
- Discovery of N-methylpiperazinyl flavones as a novel class of compounds with therapeutic potential against Alzheimer’s disease: synthesis, binding affinity towards amyloid β oligomers (Aβo) and ability to disrupt Aβo-PrPC interactions. Pure and Applied Chemistry, 91(7). View this article in WRRO
- Effect of missing data on multitask prediction methods. Journal of Cheminformatics, 10. View this article in WRRO
- Chemical Priming of Immunity without Costs to Plant Growth.. New Phytologist, 218(3), 1205-1216. View this article in WRRO
- Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction. Thrombosis and Haemostasis, 116(1), 96-102.
- OP21IDENTIFICATION OF NOVEL SMALL MOLECULE INHIBITORS OF THE FANCONI ANAEMIA DNA REPAIR PATHWAY AS A MEANS TO SENSITISES GLIOBLASTOMAS TO CHEMOTHERAPEUTIC AGENTS. Neuro-Oncology, 17(suppl 8), viii20.1-viii20.
- ChemInform Abstract: Regioselective Synthesis of 3-Aminoimidazo[1,2-a]-pyrimidines under Continuous Flow Conditions.. ChemInform, 46(16), no-no.
- Regioselective Synthesis of 3-Aminoimidazo[1,2-a]-pyrimidines under Continuous Flow Conditions. The Journal of Organic Chemistry, 79(21), 10196-10202.
- Plant perception of β-aminobutyric acid is mediated by an aspartyl-tRNA synthetase.. Nat Chem Biol, 10(6), 450-456. View this article in WRRO
- Prion chemical biology: on the road to therapeutics?. Curr Top Med Chem, 13(19), 2441-2464.
- Deconvolution of molecular targets for small molecule anti-prion compounds using proteomic and microarray techniques. PRION, 7, 66-66.
- A novel protocol to accelerate dynamic combinatorial chemistry via isolation of ligand-target adducts from dynamic combinatorial libraries: A case study identifying competitive inhibitors of lysozyme. Bioorganic and Medicinal Chemistry Letters.
- A small molecule modulator of prion protein increases human mesenchymal stem cell lifespan, ex vivo expansion, and engraftment to bone marrow in NOD/SCID mice.. Stem Cells, 30(6), 1134-1143.
- Synthesis and evaluation of 1-amino-6-halo-β-carbolines as antimalarial and antiprion agents.. ChemMedChem, 7(4), 578-586.
- Indole-3-glyoxylamides as a novel lead series against prion diseases. PRION, 6, 99-99.
- Deconvoluting molecular targets for small molecule anti-prion compounds using proteomic and microarray techniques. PRION, 6, 98-98.
- 2,4-diarylthiazole antiprion compounds as a novel structural class of antimalarial leads.. Bioorg Med Chem Lett, 21(12), 3644-3647.
- Validation of Reaction Vectors forde NovoDesign, 29-43.
- Discovery of 6-substituted indole-3-glyoxylamides as lead antiprion agents with enhanced cell line activity, improved microsomal stability and low toxicity.. Eur J Med Chem, 46(9), 4125-4132.
- Structure-activity relationship refinement and further assessment of indole-3-glyoxylamides as a lead series against prion disease.. ChemMedChem, 6(1), 115-130.
- Development of a differential scanning fluorimetry based high throughput screening assay for the discovery of affinity binders against an anthrax protein.. J Pharm Biomed Anal, 52(5), 802-808.
- Inside Cover: Improved 2,4-Diarylthiazole-Based Antiprion Agents: Switching the Sense of the Amide Group at C5 Leads to an Increase in Potency (ChemMedChem 9/2010).. ChemMedChem, 5(9), 1406.
- Improved 2,4-diarylthiazole-based antiprion agents: switching the sense of the amide group at C5 leads to an increase in potency.. ChemMedChem, 5(9), 1476-1488.
- Combination Rules for Group Fusion in Similarity-Based Virtual Screening. MOL INFORM, 29(6-7), 533-541.
- Ligand-based virtual screening using Bayesian networks.. J Chem Inf Model, 50(6), 1012-1020. View this article in WRRO
- ChemInform Abstract: Ugi Reactions with Ammonia Offer Rapid Access to a Wide Range of 5-Aminothiazole and Oxazole Derivatives.. ChemInform, 41(5).
- ChemInform Abstract: Exploring Catalyst and Solvent Effects in the Multicomponent Synthesis of Pyridine-3,5-dicarbonitriles.. ChemInform, 41(5).
- SPR biosensor as a tool for screening prion protein binders as potential antiprion leads.. Methods Mol Biol, 627, 147-155.
- Design, synthesis, and structure-activity relationship of indole-3-glyoxylamide libraries possessing highly potent activity in a cell line model of prion disease.. J Med Chem, 52(23), 7503-7511.
- ChemInform Abstract: Development of a Diversity-Oriented Approach to Oxazole-5-amide Libraries.. ChemInform, 40(40).
- Exploring catalyst and solvent effects in the multicomponent synthesis of pyridine-3,5-dicarbonitriles.. J Org Chem, 74(18), 6999-7006.
- Ugi reactions with ammonia offer rapid access to a wide range of 5-aminothiazole and oxazole derivatives.. J Org Chem, 74(18), 7084-7093.
- Knowledge-based approach to de novo design using reaction vectors.. J Chem Inf Model, 49(5), 1163-1184.
- Development of a diversity-oriented approach to oxazole-5-amide libraries.. J Org Chem, 74(10), 3856-3865.
- Evaluation of a Bayesian inference network for ligand-based virtual screening.. J Cheminform, 1(1), 5. View this article in WRRO
- Regioselective, Solvent-Free Synthesis of 3-Aminoimidazo[1,2-a]pyrimidines Under Microwave Irradiation Promoted by Zeolite HY. SYNLETT(20), 3183-3187.
- ChemInform Abstract: Versatile Assembly of 5-Aminothiazoles Based on the Ugi Four-Component Coupling.. ChemInform, 39(49).
- Versatile assembly of 5-aminothiazoles based on the Ugi four-component coupling. TETRAHEDRON LETT, 49(36), 5324-5327.
- Synthesis and evaluation of a focused library of pyridine dicarbonitriles against prion disease.. Eur J Med Chem, 43(1), 93-106.
- Mechanistic studies leading to a new procedure for rapid, microwave assisted generation of pyridine-3,5-dicarbonitrile libraries. TETRAHEDRON, 63(24), 5300-5311.
- Library synthesis and screening: 2,4-diphenylthiazoles and 2,4-diphenyloxazoles as potential novel prion disease therapeutics.. J Med Chem, 50(6), 1347-1353.
- Evaluation of machine-learning methods for ligand-based virtual screening.. J Comput Aided Mol Des, 21(1-3), 53-62. View this article in WRRO
- Unexpected Formation of N,N-Disubstituted Formamidines from Aromatic Amines, Formamides and Trifluoroacetic Anhydride.. ChemInform, 37(43).
- Synthesis and SAR study of acridine, 2-methylquinoline and 2-phenylquinazoline analogues as anti-prion agents.. Eur J Med Chem, 41(10), 1124-1143.
- Synthesis of 5-Aminothiazoles as Building Blocks for Library Synthesis.. ChemInform, 37(29).
- Synthesis of 5-aminothiazoles as building blocks for library synthesis. TETRAHEDRON LETT, 47(14), 2361-2364.
- Screening a library of potential prion therapeutics against cellular prion proteins and insights into their mode of biological activities by surface plasmon resonance.. J Pharm Biomed Anal, 40(4), 822-832.
- Knowledge-based interaction fingerprint scoring: a simple method for improving the effectiveness of fast scoring functions.. J Chem Inf Model, 46(2), 686-698.
- Virtual screening using binary kernel discrimination: effect of noisy training data and the optimization of performance.. J Chem Inf Model, 46(2), 478-486.
- Library design, synthesis, and screening: pyridine dicarbonitriles as potential prion disease therapeutics.. J Med Chem, 49(2), 607-615.
- Unexpected formation of N,N-disubstituted formamidines from aromatic amines, formamides and trifluoroacetic anhydride. Tetrahedron, 62(24), 5617-5625.
- Ligand-based virtual screening using binary kernel discrimination. MOL SIMULAT, 31(8), 597-604. View this article in WRRO
- Retrospective docking study of PDE4B ligands and an analysis of the behavior of selected scoring functions.. J Chem Inf Model, 45(4), 1061-1074.
- Predicted consequences of site-directed mutagenesis and the impact of species variation on prion protein misfolding through the N-terminal domain. Journal of Molecular Modeling, 11(6), 468-473.
- Identification of mammalian species using genosensors. Bioelectrochemistry, 67(2 SPEC. ISS.), 163-169.
- Prion therapeutics from traditional Chinese herbs. MOLECULAR & CELLULAR PROTEOMICS, 3(10), S45-S45.
- Prostate-specific antigen (PSA)-mediated proliferation, androgenic regulation and inhibitory effects of LY312340 in HOS-TE85 (TE85) human osteosarcoma cells. Anticancer Research, 22(5), 2725-2732.
- Molecular Recognition: Design of “Keys”. Combinatorial Chemistry & High Throughput Screening, 5(6), 409-427.
- Rational Design of a Polymer Specific for Microcystin-LR Using a Computational Approach. Analytical Chemistry, 74(6), 1288-1293.
- Design, Synthesis, and Proposed Active Site Binding Analysis of Monocyclic 2-Azetidinone Inhibitors of Prostate Specific Antigen. Journal of Medicinal Chemistry, 44(10), 1491-1508.
- Chemical Grafting of Molecularly Imprinted Homopolymers to the Surface of Microplates. Application of Artificial Adrenergic Receptor in Enzyme-Linked Assay for β-Agonists Determination. Analytical Chemistry, 72(18), 4381-4385.
- “Bite-and-Switch” Approach to Creatine Recognition by Use of Molecularly Imprinted Polymers. Advanced Materials, 12(10), 722-724.
- In Vitro Diagnostics in Diabetes: Meeting the Challenge. Clinical Chemistry, 45(9), 1596-1601.
- The synthesis and screening of a combinatorial peptide library for affinity ligands for glycosylated haemoglobin1This paper was a finalist for the Biosensors & Bioelectronics Award for the most original contribution to the Congress, but was withdrawn from the competition by the authors.1. Biosensors and Bioelectronics, 13(7-8), 779-785.
- Design and synthesis of novel monocyclic β-lactam inhibitors of prostate specific antigen. Bioorganic & Medicinal Chemistry Letters, 7(13), 1689-1694.
- Stereochemistry of the enzymic lactonisation of cis,cis-muconic and 3-methyl-cis,cis-muconic acid. Journal of the Chemical Society, Perkin Transactions 1(11), 1153-1153.
- ChemInform Abstract: Design and Synthesis of Novel Monocyclic β-Lactam Inhibitors of Prostate Specific Antigen.. ChemInform, 28(46), no-no.
- ChemInform Abstract: Stereochemistry of the Enzymic Lactonization of cis,cis-Muconic and 3- Methyl-cis,cis-muconic Acid.. ChemInform, 27(36), no-no.
- Thiazoles, Comprehensive Heterocyclic Chemistry III (pp. 635-754). Elsevier
- Thiazoles, Comprehensive Heterocyclic Chemistry III (pp. 635-754).
Conference proceedings papers
- Anti prion molecules and their interaction with amyloid beta. PRION, Vol. 7 (pp 77-77)
- De novo design of synthetically accessible compounds: Application to fragment-based drug design. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 243
- Searching putative targets in silico for anti-prion compounds. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 243
- Piezoelectric sensors based on biomimetic peptides for the detection of heat shock proteins (HSPs) in mussels. ANALYTICAL LETTERS, Vol. 39(8) (pp 1627-1642)
- Piezoelectric sensors for dioxins: a biomimetic approach. BIOSENSORS & BIOELECTRONICS, Vol. 20(6) (pp 1203-1210)
- BIOMIMETIC TRAPS FOR DIOXINS: A MIXED COMPUTATIONAL AND EXPERIMENTAL APPROACH. Sensors and Microsystems
- ‘Bite-and-Switch’ approach using computationally designed molecularly imprinted polymers for sensing of creatinine11Editors Selection. Biosensors and Bioelectronics, Vol. 16(9-12) (pp 631-637)
- Incidence of RET mutations in patients with Hirschsprung's disease. Journal of Pediatric Surgery, Vol. 35(1) (pp 139-143)
- Teaching interests
Medicinal Chemistry; Biological Chemistry.
- Teaching activities
Undergraduate and postgraduate taught modules
- Chemistry and the World Around Us (Level 1): Healthy Eating: Nutrients and Nutraceuticals
Introducing some simple chemical principles of familiar aspects of the world around us which we often take for granted and to highlight the significance of chemistry to everyday life, society, and the future of our planet.
- Introduction to Chemical Biology & Medicinal Chemistry (Level 3)
This course explores the chemical biology behind proteins, and how they can be targeted in the development of new medicinal drugs.
- Medicinal Chemistry (Year 4)
This segment introduces the main concepts, methods and limitations of the technique of modelling molecules using empirical (classical) descriptions of the interactions between atoms, functional groups and other properties of molecular fragments.
- Tutorials: Level 1 General Chemistry
- Level 3 Literature Review
- Level 2 Organic Laboratories
- Level 3 Organic Laboratories
- Level 4 Research Project
- Chemistry and the World Around Us (Level 1): Healthy Eating: Nutrients and Nutraceuticals