TILDEN LECTURE - STUDIES ON THYMIDYLATE SYNTHASE AND DIHYDROFOLATE-REDUCTASE - 2 ENZYMES INVOLVED IN THE SYNTHESIS OF THYMIDINE

The review describes the author's work on thymidylate synthase and dihydrofolate reductase. A chemical model for the synthesis of thymine followed the biological labelling results more closely than expected. Work on the enzyme dihydrofolate reductase showed a difference in docking at the active site of the enzyme between the natural substrate and the drug methotrexate. Synthesis of stereospecifically deuteriated leucine and incorporation into the enzyme allowed assignment of the diastereotopic methyl groups of the leucine residues of the enzyme in the H-1-NMR spectrum. This will be generally applicable to other proteins.