Dr. Beining Chen

Biographical Sketch

After a BSc (1984) and MSc (1987) in China, dr. 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 is currently a Reader.

Research Keywords

Molecular modelling, combinatorial chemistry, medicinal chemistry, molecular recognition, biological chemistry, prion protein

Teaching Keywords

Medicinal Chemistry; Biological Chemistry

Selected Publications:

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, Zheng Fang, Wei He, Xin Li, Zhengjiang Li, Beining Chen, Pingkai Ouyang and Kai Guo, Bioorg. Med. Chem. Lett. 2013, 23, 5174-7.
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, Sindhu T. Mohanty, Claire J. Cairney, Andrew D. Chantry, Sanjeev Madan, James A. Fernandes, Steven J. Howe, Harry D. Moore, Mark J. Thompson, Beining Chen, Adrian Thrasher, W. Nicol Keith and Ilaria Bellantuono, Stem Cells 2012, 30, 1134-1143.
Structure-Activity Relationship Refinement and Further Assessment of Indole-3-glyoxylamides as a Lead Series against Prion Disease, Mark J. Thompson, Jennifer C. Louth, Steven Ferrara, Fiona J. Sorrell, Benjamin J. Irving, Edward J. Cochrane, Anthony J. H. M. Meijer and Beining Chen, Chemmedchem 2011, 6, 115-130.
Development of a differential scanning fluorimetry based high throughput screening assay for the discovery of affinity binders against an anthrax protein, Fiona J. Sorrell, Gemma K. Greenwood, Kristian Birchall and Beining Chen, J. Pharm. Biomed. Anal. 2010, 52, 802-808.
Design, Synthesis, and Structure-Activity Relationship of Indole-3-glyoxylamide Libraries Possessing Highly Potent Activity in a Cell Line Model of Prion Disease, Mark J. Thompson, Vinciane Borsenberger, Jennifer C. Louth, Katie E. Judd and Beining Chen, J. Med. Chem. 2009, 52, 7503-7511.
Ugi Reactions with Ammonia Offer Rapid Access to a Wide Range of 5-Aminothiazole and Oxazole Derivatives, Mark J. Thompson and Beining Chen, J. Org. Chem. 2009, 74, 7084-7093.
Knowledge-Based Approach to de Novo Design Using Reaction Vectors, Hina Patel, Michael J. Bodkin, Beining Chen and Valerie J. Gillet, J Chem Inf Model 2009, 49, 1163-1184.
Library synthesis and screening: 2,4-diphenylthiazoles and 2,4-diphenyloxazoles as potential novel prion disease therapeutics, William Heal, Mark J. Thompson, Roger Mutter, Hannah Cope, Jenny C. Louth and Beining Chen, J. Med. Chem. 2007, 50, 1347-1353.
Screening a library of potential prion therapeutics against cellular prion proteins and insights into their mode of biological activities by surface plasmon resonance, F. Touil, S. Pratt, R. Mutter and B. N. Chen, J. Pharm. Biomed. Anal. 2006, 40, 822-832.
Virtual screening using binary kernel discrimination: Effect of noisy training data and the optimization of performance, B. N. Chen, R. F. Harrison, K. Pasupa, P. Willett, D. J. Wilton, D. J. Wood and X. Q. Lewell, J Chem Inf Model 2006, 46, 478-486.
Library design, synthesis, and screening: Pyridine dicarbonitriles as potential prion disease therapeutics, T. R. K. Reddy, R. Mutter, W. Heal, K. Guo, V. J. Gillet, S. Pratt and B. Chen, J. Med. Chem. 2006, 49, 607-615.

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.

A. Therapeutics

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 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.

B. 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 Dr. Chen's group for the prediction of abnormal prion structures.

Teaching Section

Organic Chemistry

Undergraduate Courses Taught

An Introduction to Biology for Physical Scientists (Year 1)
This course provides a basic knowledge and understanding of the occurrence, structure and function of important types of biopolymers such as proteins and nucleic acids, their organisation into biomaterials and their function in living systems.
Introduction to Medicinal Chemistry (Year 3)
Medicinal chemistry is a chemistry based discipline, involving aspects of biological, medical and pharmaceutical sciences. It is concerned with the invention, discovery, design, identification and preparation of biologically active compounds, the study of their metabolism, the interpretation of their mode of action at the molecular level and the construction of structure-activity relationships. The general principles and challenges involved in medicinal chemistry will be discussed.
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.

Postgraduate Courses Taught

Biopolymers and Biomaterials B

Tutorial & Workshop Support

First Year General Tutorials.
Second Year Organic Chemistry Tutorials.
Third Year Workshops (Introduction to Medicinal Chemistry).
Third Year Literature Review.
Fourth Year Workshops (Medicinal Chemistry).

Laboratory Teaching

First Year Demonstrating
Second Year Demonstrating
Fourth Year Research Project

Reader in Medicinal Chemistry