Research

The Biological Chemistry group focuses on problems at the interface of chemistry, biology, physics, engineering and medicine with particular strengths in biocatalysis, mechanistic enzymology, bioorganic and bioinorganic chemistry, synthetic biology, biomolecular interactions, biomolecular NMR spectroscopy and mass spectrometry, biophotonics and optogenetics, organic synthesis and medicinal chemistry.

Enzyme catalysis

Our research goals are to probe enzymatic reaction mechanisms, elucidating the role of protein dynamics and quantum mechanical effects in catalysis, and tailoring substrate selectivity for synthetic chemistry purposes.

Current projects include:

• Enzymology of terpenoid biosynthesis and synthetic biology approaches for expansion of the pool of these secondary metabolites to include novel terpenoid-like compounds with applications as drugs and crop protection agents
• Combined experimental and theoretical investigations of the role of protein motions and hydride tunnelling in enzyme catalysis, using dihydrofolate reductase as a model system
• Studies of enzymes involved in antibiotic resistance or which could be novel targets for antibiotics

Manipulating biomolecular interactions including biophotonics and optogenetics

Our aims are to control interactions between biomolecules by inducing conformational switching using small molecules or light.

Current projects include:

• Photonic control of protein-protein interactions to regulate the apoptotic pathway in cells
• Chemical and enzymatic synthesis of flavins and their analogues and application of these cofactors in protein photoswitches for synthetic biology
• Controlling interactions of RNA molecules in cells using peptides and nucleic acid analogues
• Investigation of the immunogenic properties of cyclic peptides with potential applications in anti-cancer vaccines

Biomolecular NMR spectroscopy and mass spectrometry

NMR work is performed using our flagship 600 MHz Bruker NMR spectrometer equipped with a quadruple resonance QCI cryoprobe, as well as national high-field NMR facilities. Mass spectrometry studies benefit heavily from our Waters Synapt ion mobility mass spectrometer.

Current projects include:

• NMR investigations of protein structure and dynamics in response to environmental changes
• NMR studies of amyloid-beta peptides (the causative agents of Alzheimer's Disease) in complex with metal ions
• Mass spectrometry tools for structural elucidation of cyclic peptides

Organic synthesis and medicinal chemistry

Much attention within the section is focused on the synthesis of compounds with important biological properties, which complement our interests in enzyme catalysis.

Current projects include:

• Synthetic precursor or intermediate analogues for terpene synthases, to generate expanded product diversity (including novel artemisinin analogues active against malaria) or to probe the reaction mechanism
• Development of inhibitors of the enzyme calpain-1, a potential target for anti-inflammatory therapy in diseases such as rheumatoid arthritis
• Studies of the synthesis and biosynthesis of novel antibiotics

Find out more details of group members specific research interests by looking at their individual profiles under the  people tab.