Cardiff School of Chemistry

Additional Information

Dipl. Chem. ETH (B.Sc.), Eidgenössische Technische Hochschule (ETH), Zürich (1985). PhD Harvard University / ETH Zürich (1988).  Postdoctoral Research Fellow, National Institute for Medical Research, Mill Hill (1988, P. W. J. Rigby) Habilitation, Department of Chemistry, ETH Zürich (1999). Senior Lecturer in Chemistry, University of Birmingham (1999-2001). Professor of Chemical Biology, University of Birmingham (2001-2004). Appointed as Distinguished Research Professor, Cardiff in 2005.

Research Interests

Physical and Chemical Basis of Enzyme Catalysis

Enzymes are characterised by their high chemical selectivity and specificity as well as by the enormous rate accelerations relative to the uncatalysed reactions.

• Sequiterpene synthases are studied as a typical example of the generation of molecular diversity from a single precursor by a large family of structurally related enzymes. A variety of techniques from synthetic, physical organic and computational chemistry as well as from biochemistry are used.
• The physical and chemical basis of enzyme catalysis. It has long been accepted that electrons can be transferred in chemical reactions by quantum mechanical tunnelling with energies of activation deriving from heavy-atom motions. However, only recently have several cases of hydrogen tunnelling been described. In these cases protein motions often promote the reaction. The mechanism by which such reactions occur is addressed using chemical, computational and biophysical methods including NMR spectroscopy and X-ray crystallography.

Synthetic Biology

This is a particularly exciting time to be working in the area of protein science. Recent advances in genomics and proteinomics are providing a wealth of protein sequences and three dimensional structures at an ever-increasing speed. Together with new insights into the molecular mechanisms of action brought about by fundamental studies, this explosion of data has helped us gain a deeper understanding of the relationship between protein sequence, structure and function. It is now becoming increasingly possible to design peptides and proteins that are tailor made to carry out a variety of tasks. The new discipline of Synthetic Biology capitalises on these advances. It aims to design and construct new biological components, devices and system and redesign existing, natural biological systems for useful purposes.

• Miniature enzymes. De novo designed proteins are not only a rigorous test of our understanding of natural biomacromolecules but they should also shed new light on the molecular mechanisms employed by proteins and allow us to design proteins with functions unprecedented in nature.

• Photonic Control of Biomacromolecular Function. Many biological processes depend on protein-protein and protein-DNA interactions. These interactions, which are inherently difficult to target with small molecules, often rely on small protein segments such as a-heclices. We are developing methodology to use small peptides that can be activated with external light pulses, to control such interactions involved in biological processes like gene expression and cell proliferation. A multidisciplinary approach is used bringing together chemist, physicists, biochemists and molecular and cellular biologists.

Organic Synthesis

The study of enzyme structure and function often requires the synthesis of small molecules as probes. Hence organic synthesis directed at producing bioactive molecules is an active line of research. Currently we are using a Diversity Oriented Synthesis (DOS) approach to prepare modified sesquiterpene precursors and are also undertaking synthesis of carbohydrate derivatives in order to study their effects upon protein folding and stability. 

Further Information

Selected Publications

Lucia Guerrero, Oliver S. Smart, Chris J. Weston, Darcy C. Burns, G. Andrew Woolley, Rudolf K. Allemann, Photochemical Regulation of DNA-Binding Specificity of MyoD, Angewandte Chemie International Edition 44 (2005) 7778, doi:10.1002/anie.200502666

E. Turner, C. Cureton, C. Weston, O. Smart, R. Allemann, Controlling the DNA Binding Specificity of bHLH Proteins through Intramolecular Interactions., Chemistry & Biology 11 (2003) 69, doi:10.1016/j.chembiol.2003.12.015

Melanie J. Calvert, Peter R. Ashton, and Rudolf K. Allemann, Germacrene A Is a Product of the Aristolochene Synthase-Mediated Conversion of Farnesylpyrophosphate to Aristolochene, J. Am. Chem. Soc. 124 (2002) 11636, doi:10.1021/ja020762p

Giovanni Maglia and Rudolf K. Allemann, Evidence for Environmentally Coupled Hydrogen Tunneling during Dihydrofolate Reductase Catalysis, J. Am. Chem. Soc. 125 (2003) 13372, doi:10.1021/ja035692g