Picking pockets to fuel antimicrobial drug discovery.
The inhibition of essential enzymes in microbial pathogens offers a route to treatment of infectious diseases. However, although the biology of the organism dictates a need for a particular enzyme activity, this does not necessarily mean that the enzyme is a good drug target. The chemistry of the active site (size, shape and properties) determines the likelihood of finding a molecule with the right properties to influence drug discovery. Discriminating between good and less-good targets is important. Studies on enzymes involved in the regulation of oxidative stress and pterin/folate metabolism of trypanosomatid parasites and isoprenoid precursor biosynthesis in bacteria and apicomplexan parasites illustrates a range of active sites representing those that are challenging with respect to the discovery of potent inhibitors, to others that provide more promising opportunities in drug discovery.
Hunter
W N
WN
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Tayside, Scotland, U.K. w.n.hunter@dundee.ac.uk
D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D008958:Models, Molecular; D010088:Oxidoreductases / Q000378:metabolism
D000890:Anti-Infective Agents; D010088:Oxidoreductases; C085592:pteridine reductase