Latent inhibitors. Part 5. Latent inhibition of dihydrofolate reductase by a pteridine-spiro-cyclopropane
- 1 January 1989
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Journal of the Chemical Society, Perkin Transactions 1
- No. 7,p. 1297-1304
- https://doi.org/10.1039/p19890001297
Abstract
The design of cyclopropane-containing enzyme activated inhibitors of dihydrofolate reductase is presented. The synthesis of two examples, 2-amino-7,8-dihydro-6-hydroxymethylpteridine-7-spirocyclopropan-4(3H)-one and 2,4-diamino-5-(4-chlorophenyl)-6-cyclopropylpyrimidine, is described. Kinetic studies with dihydrofolate reductase from E. coil are presented to show that the former is a time-dependent inhibitor of the enzyme whereas the latter is a typical competitive inhibitor. The results are interpreted with regard to the active site structure of dihydrofolate reductase.This publication has 14 references indexed in Scilit:
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