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The Potential Role of Solvation in the Dihydrofolate Reductase Species Selectivity of Trimethoprim

  • Lee F. Kuyper

Abstract

Trimethoprim (1, TMP) is an important antibacterial agent (Finland et al., 1982) that exerts its activity through the inhibition of the enzyme dihydrofolate reductase (DHFR) (Hitchings, 1983). DHFR catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate. The latter substance is important to the biosynthesis of purines, pyrimidines and several of the amino acids and is therefore necessary for normal cell function (Blakley, 1984). DHFR is a ubiquitous protein, found not only in bacteria but also man, and one of the unique properties of TMP is its ability to inhibit selectively the bacterial species of the enzyme (Roth, 1983; Hitchings et. al., 1988). That remarkable selectivity is illustrated in Table 1.

Keywords

Methoxy Group Dihydrofolate Reductase Pyrimidine Ring Inhibition Data Enzyme Dihydrofolate Reductase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag New York, Inc. 1990

Authors and Affiliations

  • Lee F. Kuyper

There are no affiliations available

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