Diastereoisomers of Formaldehyde Derivatives of Tetrahydrofolic Acid and Tetrahydroaminopterin

S. B. Horwitz, G. Kwok, L. Wilson, R. L. Kisliuk

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Previous work on the diethylaminoethylcellulose chromatography of CH2O derivatives of tetrahydrofolic acid leading to the isolation of diastereoisomers, designated as 5,10-methylene derivatives, was repeated using formaldehyde-14C. The isolated material contained 0.7-0.8 mole of formaldehyde/mole of tetrahydrofolate rather than 1 required for the 5,10-methylene structure. This finding was verified by chemical determination of CH2O on the isolated material. Comparable experiments with CH2O derivatives of tetrahydroaminopterin yielded 0.7 mole of CH2O/mole of tetrahydropteridine. These results suggest that the compounds designated as diastereoisomers of 5,10-methylenetetrahydrofolate are actually complexes which contain 4 molecules of tetrahydropteridine and 3 molecules of formaldehyde. The diastereoisomer complex of CH2O and tetrahydroaminopterin corresponding chromatographically to the diastereoisomer complex of CH2O and tetrahydrofolate, which is biologically active, was more inhibitory to the growth of Pediococcus cerevisiae and Streptococcus faecalis than that corresponding to the biologically inactive diastereoisomer complex of formaldehyde and tetrahydrofolate. When the diastereoisomer complexes of tetrahydroaminopterin were combined a synergistic effect on growth inhibition was obtained. Each diastereoisomer complex inhibited mouse tumor dihvdrofolate reductase to the same extent. Neither diastereoisomer complex showed significant inhibition of Escherichia coli thymidylate synthetase.

Original languageEnglish (US)
Pages (from-to)49-51
Number of pages3
JournalJournal of Medicinal Chemistry
Volume12
Issue number1
DOIs
StatePublished - Jan 1 1969
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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