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Medicinal Chemistry - Research
The Department of Medicinal Chemistry has a major research focus in the area of drug design and development, which is supported by contributions in the fields of:
Medicinal Chemistry as a discipline focuses on drug design and development. This process typically involves elucidation of the 3D structure of proteins and, in particular, an active site by which biochemical processes may take place. This can be achieved using techniques such as protein purification, NMR spectroscopy, protein X-ray crystallography and mass spectrometry. Once an active site of a protein is better understood, computer-aided molecular design may be employed to design a drug candidate that effectively interacts at the active site. The best candidates can be synthesized in a laboratory using a range of classical and modern reactions. Once synthesized and purified (using for example, HPLC), the structure of these new chemical entities can be characterised by a host of techniques including NMR spectroscopy, small molecule X-ray crystallography and mass spectrometry.
The design of new lead compounds has become or fundamental importance to many of the Department’s projects and is carried out by three principal techniques:
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receptor-based design, in which the known three-dimensional structure of a target receptor is used to design compounds to interact with the macromolecule. For example a project that involved the computer-assisted design of selective inhibitors for a protein of known structure on the surface of the influenza virus, led to the discovery of the anti influenza drug Relenza.
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mechanism-based design, in which the known or anticipated catalytic mechanism of a target enzyme is used to design enzyme-selective inhibitors. Some examples are the design of inhibitors of the plant and bacterial enzyme PABA synthase and sialyltransferases, which have been cloned by the protein chemistry group, and modelling studies of reductases and sialidases.
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analogue-based design starts from the structures of known drugs and uses computer techniques to determine the structural features necessary for biological activity. Analogues with potential for enhanced activity may then be designed. This approach is being used to develop novel antipsychotic drugs and antiviral agents.
A wide range of facilities is thus required, given the depth and breadth of medicinal chemistry. Various equipment and laboratory-based facilities as described in the facilities section sustain the research strengths of the Department.
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