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:

Development of a differential scanning fluorimetry based high throughput screening assay for the discovery of affinity binders against an anthrax protein, F. J. Sorrell, G. K. Greenwood, K. Birchall and B. N. 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, M. J. Thompson, V. Borsenberger, J. C. Louth, K. E. Judd and B. N. Chen, J. Med. Chem. 2009, 52, 7503-7511.
Exploring Catalyst and Solvent Effects in the Multicomponent Synthesis of Pyridine-3,5-dicarbonitriles, K. Guo, M. J. Thompson and B. N. Chen, J. Org. Chem. 2009, 74, 6999-7006.
Development of a Diversity-Oriented Approach to Oxazole-5-amide Libraries, M. J. Thompson, H. Adams and B. N. Chen, J. Org. Chem. 2009, 74, 3856-3865.
Ugi Reactions with Ammonia Offer Rapid Access to a Wide Range of 5-Aminothiazole and Oxazole Derivatives, M. J. Thompson and B. N. Chen, J. Org. Chem. 2009, 74, 7084-7093.
Crosslinking of the electrospun polyethylene glycol/cellulose acetate composite fibers as shape-stabilized phase change materials, C. Z. Chen, L. G. Wang and Y. Huang, Mater. Lett. 2009, 63, 569-571.
Lubrication at Physiological Pressures by Polyzwitterionic Brushes, M. Chen, W. H. Briscoe, S. P. Armes and J. Klein, Science 2009, 323, 1698-1701.
Synthesis and evaluation of a focused library of pyridine dicarbonitriles against prion disease, K. Guo, R. Mutter, W. Heal, T. R. K. Reddy, H. Cope, S. Pratt, M. J. Thompson and B. Chen, Eur J Med Chem 2008, 43, 93-106.
Versatile assembly of 5-aminothiazoles based on the Ugi four-component coupling, M. J. Thompson and B. N. Chen, Tetrahedron Lett. 2008, 49, 5324-5327.
Regioselective, Solvent-Free Synthesis of 3-Aminoimidazo[1,2-a]pyrimidines Under Microwave Irradiation Promoted by Zeolite HY, M. J. Thompson, J. M. Hurst and B. N. Chen, Syn. Lett. 2008, 20, 3183-3187.

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