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The Synthesis Of Analogs Of Toxoflavin And Fervenulin As Potential Antimetabolites, Bernadette Kuo Billings
The Synthesis Of Analogs Of Toxoflavin And Fervenulin As Potential Antimetabolites, Bernadette Kuo Billings
Theses and Dissertations
The synthesis of analogs of toxoflavin: 1,3,4,6-tetramethyl-1,5,6, 7-tetrahydropyrimido[4,5-c]-5,7-pyridazinedione; 1,6-dimethyl-3,4-diphenyl-1,5,6,7-tetrahydropyrimido[4,5-c]-5,7-pyridazinedione; 3,5,7-trimethyl-8-phenyl-2,3,4,8-tetrahydropyrido[2,3-d]-2,4-pyrimidinedione are discussed. The synthesis of analogs of fervenulin: 3,4,6-trimethyl-5,6,7,8-tetrahydropyrimido[4,5-c]-5,7-pyridazinedione; 6-methyl-3,4-diphenyl-5,6,7,8-tetrahydropyrimido[4,5-c]-5,7-pyridazinedione; 2-hydroxy-3,5,7-trimethyl-4(3H)pyrido[2,3-d]-2,4-pyrimidinone are discussed. Several intermediates have been prepared: 6 -methylamino-3-methyluracil by a new method; 6-n-propylamino-3-methyluracil: 6-n-butylamino-3-methyluracil and 3-ethyl-2-ethylthio-2-hydroxy-4(3H)pyrimidinone.
Studies Of N⁵, N¹⁰-Methylene Tetrahydrofolate Reductase From Porcine Kidney And Mouse L1210-Induced Tumor Tissues, Purification And Interaction With Antifolates, David W. Jayme
Theses and Dissertations
Methylene tetrahydrofolate reductase has been purified 1000-fold from porcine kidney and 400-fold from mouse L1210-induced tumor tissue by classical methods. The enzyme preparations have been demonstrated to be essentially free of contaminating methionine synthetase and serine transhydroxymethylase activity. Studies of the kinetic properties of the kidney and tumor enzymes, with respect to the reverse reaction using N5-methyl tetrahydrofolate as the variable substrate, have indicated Km values of 2.0 and 2.4 x 10-4 M, respectively. Inhibition of this key branch point enzyme in folate metabolism by a number of antimetabolites indicates that several of these antifolate compounds exhibit enzyme inhibition superior …