Prof. Beining Chen
Professor of Medicinal Chemistry
Telephone: +44 (0) 114 222 9467
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.
Molecular modelling, combinatorial chemistry, medicinal chemistry, molecular recognition, biological chemistry, prion protein
Medicinal Chemistry; Biological Chemistry
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.
Undergraduate and postgraduate taught modules
- de la Vega de Leon A, Chen B & Gillet V (2018) Effect of missing data on multitask prediction methods. Journal of Cheminformatics, 10. View this article in WRRO
- Buswell W, Schwarzenbacher ER, Luna E, Sellwood M, Chen B, Flors V, Pétriacq P & Ton J (2018) Chemical Priming of Immunity without Costs to Plant Growth.. New Phytologist. View this article in WRRO
- Thomas MR, Morton AC, Hossain R, Chen B, Luo L, Shahari NNBM, Hua P, Beniston RG, Judge HM & Storey RF (2016) 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.
- Butler AJE, Thompson MJ, Maydom PJ, Newby JA, Guo K, Adams H & Chen B (2014) Regioselective synthesis of 3-aminoimidazo[1,2-a]-pyrimidines under continuous flow conditions.. The Journal of Organic Chemistry, 79(21), 10196-10202.
- Luna E, van Hulten M, Zhang Y, Berkowitz O, López A, Pétriacq P, Sellwood MA, Chen B, Burrell M, van de Meene A , Pieterse CMJ et al (2014) 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
- Chen B, Thompson M, Louth J & Guo K (2013) Prion chemical biology: on the road to therapeutics?. Curr Top Med Chem, 13(19), 2441-2464.
- Jackson MP, Louth J, Thompson MJ, Ciani B & Chen B (2013) Anti prion molecules and their interaction with amyloid beta. PRION, 7, 77-77.
- Louth J, Thompson MJ, Evans C, Wright PC, Heath P, Delagadillo JMV, Gillet V & Chen B (2013) Deconvolution of molecular targets for small molecule anti-prion compounds using proteomic and microarray techniques. PRION, 7, 66-66.
- Fang Z, He W, Li X, Li Z, Ouyang P, Guo K & Chen B (2013) 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.
- Mohanty ST, Cairney CJ, Chantry AD, Madan S, Fernandes JA, Howe SJ, Moore HD, Thompson MJ, Chen B, Thrasher A , Keith WN et al (2012) 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.
- Thompson MJ, Louth JC, Little SM, Jackson MP, Boursereau Y, Chen B & Coldham I (2012) Synthesis and evaluation of 1-amino-6-halo-β-carbolines as antimalarial and antiprion agents.. ChemMedChem, 7(4), 578-586.
- Chen B (2012) Indole-3-glyoxylamides as a novel lead series against prion diseases. PRION, 6, 99-99.
- Louth J, Thompson M, Evans C, Wright P, Heath P, Delgadillo JV, Gillet V & Chen B (2012) Deconvoluting molecular targets for small molecule anti-prion compounds using proteomic and microarray techniques. PRION, 6, 98-98.
- Thompson MJ, Louth JC, Little SM, Chen B & Coldham I (2011) 2,4-diarylthiazole antiprion compounds as a novel structural class of antimalarial leads.. Bioorg Med Chem Lett, 21(12), 3644-3647.
- Hristozov D, Bodkin M, Chen B, Patel H & Gillet VJ (2011) Validation of Reaction Vectors for de Novo Design, 1076, 29-43.
- Thompson MJ, Louth JC, Ferrara S, Jackson MP, Sorrell FJ, Cochrane EJ, Gever J, Baxendale S, Silber BM, Roehl HH & Chen B (2011) 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.
- Thompson MJ, Louth JC, Ferrara S, Sorrell FJ, Irving BJ, Cochrane EJ, Meijer AJHM & Chen B (2011) Structure-activity relationship refinement and further assessment of indole-3-glyoxylamides as a lead series against prion disease.. ChemMedChem, 6(1), 115-130.
- Sorrell FJ, Greenwood GK, Birchall K & Chen B (2010) 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.
- Thompson MJ, Louth JC, Greenwood GK, Sorrell FJ, Knight SG, Adams NB & Chen B (2010) 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.
- Thompson MJ, Louth JC, Greenwood GK, Sorrell FJ, Knight SG, Adams NBP & Chen B (2010) 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.
- Chen BN, Mueller C & Willett P (2010) Combination Rules for Group Fusion in Similarity-Based Virtual Screening. MOL INFORM, 29(6-7), 533-541.
- Abdo A, Chen B, Mueller C, Salim N & Willett P (2010) Ligand-based virtual screening using Bayesian networks.. J Chem Inf Model, 50(6), 1012-1020. View this article in WRRO
- Chen B (2010) SPR biosensor as a tool for screening prion protein binders as potential antiprion leads.. Methods Mol Biol, 627, 147-155.
- Thompson MJ, Borsenberger V, Louth JC, Judd KE & Chen B (2009) 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.
- Guo K, Thompson MJ & Chen B (2009) Exploring catalyst and solvent effects in the multicomponent synthesis of pyridine-3,5-dicarbonitriles.. J Org Chem, 74(18), 6999-7006.
- Thompson MJ & Chen B (2009) Ugi reactions with ammonia offer rapid access to a wide range of 5-aminothiazole and oxazole derivatives.. J Org Chem, 74(18), 7084-7093.
- Patel H, Bodkin MJ, Chen B & Gillet VJ (2009) Knowledge-based approach to de novo design using reaction vectors.. J Chem Inf Model, 49(5), 1163-1184.
- Thompson MJ, Adams H & Chen B (2009) Development of a diversity-oriented approach to oxazole-5-amide libraries.. J Org Chem, 74(10), 3856-3865.
- Chen B, Mueller C & Willett P (2009) Evaluation of a Bayesian inference network for ligand-based virtual screening.. J Cheminform, 1(1), 5. View this article in WRRO
- Thompson MJ, Hurst JM & Chen BN (2008) Regioselective, Solvent-Free Synthesis of 3-Aminoimidazo[1,2-a]pyrimidines Under Microwave Irradiation Promoted by Zeolite HY. SYNLETT(20), 3183-3187.
- Thompson MJ & Chen BN (2008) Versatile assembly of 5-aminothiazoles based on the Ugi four-component coupling. TETRAHEDRON LETT, 49(36), 5324-5327.
- Guo K, Mutter R, Heal W, Reddy TRK, Cope H, Pratt S, Thompson MJ & Chen B (2008) Synthesis and evaluation of a focused library of pyridine dicarbonitriles against prion disease.. Eur J Med Chem, 43(1), 93-106.
- Guo K, Thompson MJ, Reddy TRK, Mutter R & Chen B (2007) Mechanistic studies leading to a new procedure for rapid, microwave assisted generation of pyridine-3,5-dicarbonitrile libraries. TETRAHEDRON, 63(24), 5300-5311.
- Heal W, Thompson MJ, Mutter R, Cope H, Louth JC & Chen B (2007) Library synthesis and screening: 2,4-diphenylthiazoles and 2,4-diphenyloxazoles as potential novel prion disease therapeutics.. J Med Chem, 50(6), 1347-1353.
- Chen B, Harrison RF, Papadatos G, Willett P, Wood DJ, Lewell XQ, Greenidge P & Stiefl N (2007) 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
- Cope H, Mutter R, Heal W, Pascoe C, Brown P, Pratt S & Chen B (2006) Synthesis and SAR study of acridine, 2-methylquinoline and 2-phenylquinazoline analogues as anti-prion agents.. Eur J Med Chem, 41(10), 1124-1143.
- Thompson MJ, Heal W & Chen BN (2006) Synthesis of 5-aminothiazoles as building blocks for library synthesis. TETRAHEDRON LETT, 47(14), 2361-2364.
- Touil F, Pratt S, Mutter R & Chen B (2006) 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.
- Mpamhanga CP, Chen B, McLay IM & Willett P (2006) Knowledge-based interaction fingerprint scoring: a simple method for improving the effectiveness of fast scoring functions.. J Chem Inf Model, 46(2), 686-698.
- Chen B, Harrison RF, Pasupa K, Willett P, Wilton DJ, Wood DJ & Lewell XQ (2006) Virtual screening using binary kernel discrimination: effect of noisy training data and the optimization of performance.. J Chem Inf Model, 46(2), 478-486.
- Reddy TRK, Mutter R, Heal W, Guo K, Gillet VJ, Pratt S & Chen B (2006) Library design, synthesis, and screening: pyridine dicarbonitriles as potential prion disease therapeutics.. J Med Chem, 49(2), 607-615.
- Mekhalfia A, Mutter R, Heal W & Chen B (2006) Unexpected formation of N,N-disubstituted formamidines from aromatic amines, formamides and trifluoroacetic anhydride. Tetrahedron, 62(24), 5617-5625.
- Chen BN, Harrison RF, Hert J, Mpanhanga C, Willett P & Wilton DJ (2005) Ligand-based virtual screening using binary kernel discrimination. MOL SIMULAT, 31(8), 597-604. View this article in WRRO
- Mpamhanga CP, Chen B, McLay IM, Ormsby DL & Lindvall MK (2005) Retrospective docking study of PDE4B ligands and an analysis of the behavior of selected scoring functions.. J Chem Inf Model, 45(4), 1061-1074.
- Molloy DP & Chen B (2005) 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.
- Mascini M, Del Carlo M, Minunni M, Chen B & Compagnone D (2005) Identification of mammalian species using genosensors. Bioelectrochemistry, 67(2 SPEC. ISS.), 163-169.
- Qiao BL & Chen BN (2004) Prion therapeutics from traditional Chinese herbs. MOLECULAR & CELLULAR PROTEOMICS, 3(10), S45-S45.
- Chen B, Piletsky S & Turner APF (2002) High molecular recognition: design of "Keys".. Combinatorial Chemistry & High Throughput Screening, 5(6), 409-427.
- Chen B, Piletsky S & Turner APF (2002) Molecular recognition: Design of "keys". Combinatorial Chemistry and High Throughput Screening, 5(6), 409-427.
- Gygi CM, Leibovitch IY, Adlington R, Baldwin JE, Chen B, Mccoull W, Pritchard GJ, Becker GW, Dixon EP, Little SP , Sutkowski DM et al (2002) 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.
- Chianella I, Lotierzo M, Piletsky SA, Tothill IE, Chen B, Karim K & Turner APF (2002) Rational design of a polymer specific for microcystin-LR using a computational approach.. Analytical Chemistry, 74(6), 1288-1293.
- Adlington RM, Baldwin JE, Becker GW, Chen B, Cheng L, Cooper SL, Hermann RB, Howe TJ, McCoull W, McNulty AM , Neubauer BL et al (2001) 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.
- Piletsky SA, Piletska EV, Chen B, Karim K, Weston D, Barrett G, Lowe P & Turner AP (2000) Chemical grafting of molecularly imprinted homopolymers to the surface of microplates. Application of artificial adrenergic receptor in enzyme-linked assay for beta-agonists determination.. Analytical Chemistry, 72(18), 4381-4385.
- Subrahmanyam S, Piletsky SA, Piletska EV, Chen B, Day R & Turner APF (2000) “Bite‐and‐Switch” Approach to Creatine Recognition by Use of Molecularly Imprinted Polymers. Advanced Materials, 12(10), 722-724.
- Turner AP, Chen B & Piletsky SA (1999) In vitro diagnostics in diabetes: meeting the challenge.. Clinical Chemistry, 45(9), 1596-1601.
- Chen B, Bestetti G, Day RM & Turner APF (1998) 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.
- Adlington RM, Baldwin JE, Chen B, Cooper SL, McCoull W, Pritchard GJ, Howe TJ, Becker GW, Hermann RB, McNulty AM & Neubauer BL (1997) Design and synthesis of novel monocyclic β-lactam inhibitors of prostate specific antigen. Bioorganic & Medicinal Chemistry Letters, 7(13), 1689-1694.
- Chen B, Kirby GW, Rao GV & Cain RB (1996) Stereochemistry of the enzymic lactonisation of cis , cis -muconic and 3-methyl- cis , cis -muconic acid. Journal of the Chemical Society Perkin Transactions 1, 0(11), 1153-1156.
Conference proceedings papers
- Gillet VJ, Allen B, Bodkin M, Chen B, Cole J, Hristozov D, Liebeschuetz J & Patel H (2012) De novo design of synthetically accessible compounds: Application to fragment-based drug design. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 243
- Valencia J, Chen B & Gillet V (2012) Searching putative targets in silico for anti-prion compounds. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 243
- Mascini M, Del Carlo M, Compagnone D, Cozzani I, Tiscar PG, Mpamhanga CP & Chen B (2006) Piezoelectric sensors based on biomimetic peptides for the detection of heat shock proteins (HSPs) in mussels. ANALYTICAL LETTERS, Vol. 39(8) (pp 1627-1642)
- Mascini M, Macagnano A, Monti D, Del Carlo M, Paolesse R, Chen B, Warner P, D'Amico A, Di Natale C & Compagnone D (2004) Piezoelectric sensors for dioxins: a biomimetic approach. BIOSENSORS & BIOELECTRONICS, Vol. 20(6) (pp 1203-1210)
- Subrahmanyam S, Piletsky SA, Piletska EV, Chen B, Karim K & Turner APF (2001) ‘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)
- Sancandi M, Ceccherini I, Costa M, Fava M, Chen B, Wu Y, Hofstra R, Laurie T, Griffths M, Burge D & Tam PKH (2000) Incidence of RET mutations in patients with Hirschsprung's disease. Journal of Pediatric Surgery, Vol. 35(1) (pp 139-143)