Major objectives of this research are to(1) isolate loo mg of homogeneous dihydrofolate reductase (DHFR) from Candida albicans,(2) crystallize the enzyme, and(3) determine its three-dimensional structure using X-ray diffraction methods.Armed with the resulting detailed knowledge of the geometrica and topograp ica properties of Candidas DHFR in relation to the known structure of the corresponding vertebrate enzyme, Agouron Technology will design specific, pharmacologically active inhibitors that selectively cripple the bacterial reductase without interfering with one-carbon metabolism in the host. Such novel inhibitors will address the current need for new anti-infective agents with eniance anti-Candidal activity against Candida albicans.National Institute of Allergy and Infectious Diseases (NIAID)
