198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

Directional Aspects of Intermolecular Interactions 43
coenzyme used in the synthesis of thymidylate, inosinate, and methionine.
Methotrexate is an antimetabolite that is a folate analogue, and is used as a cancer
chemotherapeutic agent. It inhibits dihydrofolate reductase by binding tightly
and thereby causing a cellular deficiency of thymidylate (“thymine-less
death”) so preventing DNA synthesis. Folate and methotrexate differ by the substitution
of the pterin ring carbonyl in folate by an amino group, and by methylation
of an exocyclic folate NH-group, as shown in Fig. 35. Thus the hydrogen
a
b
Fig. 35 a, b. Action of dihydrofolate reductase [89, 90]: a formulae of dihydrofolate and methotrexate;
b stereochemistry of the enzyme action (THF = tetrahydrofolate, MTX = methotrexate)