Professor of Organic and Biological Chemistry and Head of Section

B.Sc., D.Phil. (Oxford).

Tel: 0116 252 2130

email: pmc@le.ac.uk

Research Interests

Areas of research interests cover chemical biology and mechanistic organic chemistry. Each of these areas will involve synthetic chemistry, including experience of spectroscopic methods especially high field nmr, aimed at understanding the mechanism of important chemical and biological reactions. The Biological Chemistry Group collaborates extensively within the Centre for Chemical Biology at Leicester.

Molecular Recognition

The specific ways in which molecules interact non-covalently is fundamental to many key chemical and biological phenomena, e.g. asymmetric reactions, regio- and stereoselective enzymic reactions, antibody/antigen recognition etc. The Group Research is broadly in the field of molecular recognition and covers a number of different fields.

Drug Delivery and Targeting

We have a programme of research into the design and synthesis of potent anticancer agents, particularly DNA alkylating agents, based upon the naturally occuring polyamines, spermidine and spermine. The presence of the polyamine promotes cellular uptake as well as ensuring a high affinity for the intracellular target, DNA. A major effort is also underway to probe the mechanism of cellular uptake of polyamines (Figure 1 below).

Enzyme Mechanism & Biotransformations

Studies on enzyme structure, function and mechanism include those involved in hydrogen transfer reactions thought to proceed via quantum tunnelling such as aromatic amine dehydrogenase (in collaboration with Professor Nigel Scrutton, University of Manchester ) and enzymes that catalyse useful biotransformations (cytochrome P450, ascorbate peroxidase in collaboration with Professor Gordon Roberts and Prof Emma Raven). Each of these enzymes is of potential industrial importance. The design and synthesis of potent inhibitors form an important part of this programme. More recently we have also become interested in the potential for using enzymes in organic synthesis and in their mode of action in non-aqueous solutions.

Displacement Reactions at Phosphorus

Many key reactions in biological systems involve displacement reactions at phosphorus, e.g. DNA and RNA synthesis, phosphotransferases, nucleases. Studies of the fundamental mechanisms of these reactions using stereochemical methods are being pursued, including studies on key enzyme catalysed displacement reactions such as kinases and phosphatases.

Radiation-Induced Damage to DNA

Biological systems are extremely sensitive to ionising radiation and much recent attention has been given to low level radiation in the environment as a probable cause of cancer. We have been studying the mechanisms by which ionising radiation gives rise to damage to DNA via radical reactions. The project includes the synthesis of molecules of high affinity for DNA as modifiers of radiation damage (radiosensitisers and radio-protection agents).

Selected Publications

1. Heyes, Derren J.; Quinn, Anne-Marie; Cullis, Paul M.; Lee, Michael; Munro, Andrew W.; Scrutton, Nigel S.   Internal electron transfer in multi-site redox enzymes is accessed by laser excitation of thiouredopyrene-3,6,8-trisulfonate (TUPS).    Chemical Communications  (2009),   (9),  1124-1126. 

2. Hothi, Parvinder; Hay, Sam; Roujeinikova, Anna; Sutcliffe, Michael J.; Lee, Michael; Leys, David; Cullis, Paul M.; Scrutton, Nigel S.   Driving force analysis of proton tunnelling across a reactivity series for an enzyme-substrate complex.    ChemBioChem  (2008),  9(17),  2839-2845.  

3. Hothi, Parvinder; Lee, Michael; Cullis, Paul M.; Leys, David; Scrutton, Nigel S.   Catalysis by the Isolated Tryptophan Tryptophylquinone-Containing Subunit of Aromatic Amine Dehydrogenase Is Distinct from Native Enzyme and Synthetic Model Compounds and Allows Further Probing of TTQ Mechanism.    Biochemistry  (2008),  47(1),  183-194. 

4. Abbott, Andrew P.; Cullis, Paul M.; Gibson, Manda J.; Harris, Robert C.; Raven, Emma.   Extraction of glycerol from biodiesel into a eutectic based ionic liquid.    Green Chemistry  (2007),  9(8),  868-872. 

5. Hothi, Parvinder; Roujeinikova, Anna; Khadra, Khalid Abu; Lee, Michael; Cullis, Paul; Leys, David; Scrutton, Nigel S.   Isotope Effects Reveal That Para-Substituted Benzylamines Are Poor Reactivity Probes of the Quinoprotein Mechanism for Aromatic Amine Dehydrogenase.    Biochemistry  (2007),  46(32),  9250-9259. 

6. Laventine, Dominic M.; Jenkins, Paul R.; Cullis, Paul M..  A ring-closing metathesis route to 7-membered aza-heteroannulated sugars.    Tetrahedron Letters  (2005), 46(13),  2295-2298.