Chemical Biology/Biophysics/Pharmaceutical Chemistry
Key staff: Professor Babur Chowdhry
Two principle approaches are used by this research group: experimental spectroscopic/calorimetric techniques and theoretical/computational analytical methodologies. The aforementioned experimental techniques are used to investigate both synthetic and biological (including cellular) systems from a structural, thermodynamic and/or functional viewpoint.
Quantitative and qualitative investigations use both wet chemical/biochemical and contemporary analytical techniques. Spectroscopic techniques include Raman, infra-red, nuclear magnetic resonance and photon correlation spectroscopies. These techniques give an insight into the structure of the molecules of interest, as well as their size, shape and orientation.
Calorimetric techniques include high-sensitivity differential scanning calorimetry (HSDSC) and isothermal titration calorimetry (ITC). These techniques provide thermodynamic and kinetic data relating to proteins, nucleic acids and model membrane systems, as well as biopolymer-ligand interactions, respectively.
Key external academic collaborators include:
- Professor R. Withnall (Brunel University: vibrational spectroscopy);
- Dr T. J. Dines (Dundee University: ab initio theoretical calculations);
- Dr R. Palmer (Birkbeck College: high-resolution X-ray crystallographic structures of molecules);
- Professor T. C. Jenkins (Morvus Technology Ltd: biopharmaceutics);
- Professor S. Abdali (Technical University of Denmark: Raman optical activity/vibrational circular dichroism).
Recent projects
The vibrational spectroscopic techniques, Raman and infra-red, can be used to probe organic (including drug) molecules to gain information at the atomic level. FT-Raman is being used to undertake “mapping” of solid state mixtures of molecules. Surfaceenhanced Raman spectroscopy (SERS) has been used to investigate reaction kinetics, undertake trace analysis, and is moving towards single-molecule detection. Different SERS substrates are being synthesised and investigated to enhance the capability of the SERS technique.
Experimental vibrational spectroscopic data can be compared with simulated vibrational spectra that have been determined by ab initio quantum mechanical calculations to further probe molecules and molecular interactions.
Further areas of research include studies of drug polymorphism, calorimetric analysis of nucleic acid/protein-drug interactions (including anti-cancer agents), determining the mechanism of action of osmolytes and cryoprotectants, and the physicochemical and analytical characterisation of “smart” nanoparticles, e.g. microgels as drug delivery systems.
Publications
Chowdhry, B. Z., Mendham, A. P., Tetteh, J., and Withnall, R. (2002) Kinetic resonance Raman spectroscopy of the Briggs- Rauscher oscillator. Chem. Phys. Chem., 3, pp. 443–446.
Gracia, L., Chowdhry, B. Z., and Snowden, M. J. (2006) Stabilization of Colloids by Polymers. Somasundaran, P. (ed.). Taylor and Francis.
Harding, S. E., and Chowdry, B. Z. (eds.)(2001) Protein-Ligand Interactions: Hydrodynamics and Calorimetry: A Practical Approach. Oxford: Oxford University Press.
Pinkrah, V. T., Beezer, A. E., Chowdhry, B. Z., et al. (2004) Thermodynamic considerations of microgel swelling behaviour. Langmuir, 20, pp. 8531–8536.
Potter, B., Palmer, R. A., Withnall, R., Jenkins, T. C., and Chowdhry, B. Z. (2003) Two new cyclosporin folds observed in the structures of the immunosuppressant cyclosporin G and the formyl peptide receptor antagonist cyclosporin H at ultra-high resolution. Org. Biomol. Chem., 1, pp. 1466–74.