title: A structure-based approach to drug discovery; crystallography and implications for the development of antiparasite drugs.
abstract: Advances in the life and physical sciences have enabled us to characterize the 3-dimensional structure and the biochemical or biological activity of both small and large molecules. The use of structural chemistry to assist understanding of biological activity provides information relevant to the design, development or identification of new pharmaceuticals. This structure based approach has become an important component of drug research and is in widespread use by the major pharmaceutical companies. A brief historical introduction, to convey how this area of science has reached the present stage, is given. The basis of the structural approach to understanding the chemistry of small and large molecule biological activity is outlined with an emphasis on the use of results derived from X-ray diffraction methods. Developments in other areas are discussed to emphasize the multidisciplinary nature of this research and the benefits of combining different methods. Examples of protein crystallographic studies in the area of molecular parasitology, some of which are directly relevant to antiparasite drug design, are presented. The characterization of the enzyme trypanothione reductase, a project which has benefited from many of the recent developments, is detailed. Future challenges and difficulties, both scientific and economic, are discussed.
authors.affiliation: Department of Biochemistry, University of Dundee, Scotland, UK.
authors.forename: W N
authors.initials: WN
authors.lastname: Hunter
mesh_terms: D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology; D019295:Computational Biology; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D015195:Drug Design; D004345:Drug Industry / Q000191:economics / Q000639:trends*; D015801:Helminth Proteins / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry
chemical_list: D000977:Antiparasitic Agents; D015801:Helminth Proteins; D015800:Protozoan Proteins; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase