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Rapid determination of thymidylate synthase activity and its inhibition in intact L1210 leukemia cells in vitro.
There was a good correlation between tritium release, cellular uptake, and incorporation of [2-14C]dUrd into DNA, suggesting that competition for uptake and/or phosphorylation may contribute to the overall effects of certain nucleoside analogues on cellular dTMP synthase activity measured using the tritanium release assay. Expand
Calorimetric studies of ligand binding in R67 dihydrofolate reductase.
A role for the O4 atom of folate in a pairing preference with NADPH, which ultimately facilitates catalysis is suggested, indicating interligand pairing preferences. Expand
Inhibition of gamma-glutamyl hydrolases in human cells by 2-mercaptomethylglutaric acid.
It is demonstrated that inhibition of gamma-glutamyl hydrolases is an effective approach to alter the distribution of polyglutamate forms of methotrexate in vivo and indicated that enzymatic hydrolysis may contribute to regulation of polyGLutamate chain lengths in human cells. Expand
Synthesis of a Novel Antiretroviral Thymidine Analog: 1-(2-Deoxy-β-D-ribofuranosyl)-4-acetylimidazolin-2-one (Imidine)
Abstract The total synthesis of imidine (8), a novel isomer of thymidine is described. Depending on the coupling method used, either the anomeric mixture of the protected desired nucleoside, or theExpand
  • T. Kalman, Li Lai
  • Chemistry, Medicine
  • Nucleosides, nucleotides & nucleic acids
  • 1 April 2005
A combination of mechanism-based and structure-based design strategies led to the synthesis of a series of 5- and 6-substituted uracil derivatives as potential inhibitors of thymidineExpand
Exploitation of folate and antifolate polyglutamylation to achieve selective anticancer chemotherapy
SummarySynthesis of poly(γ-glutamate) metabolites of natural folates and antifolates is a critical process. Folylpolyglutamates are essential for cell proliferation. Polyglutamates of glutamateExpand
N4-(dialkylamino)methylene derivatives of 2'-deoxycytidine and arabinocytidine: physicochemical studies for potential prodrug applications.
  • S. Kerr, T. Kalman
  • Chemistry, Medicine
  • Journal of pharmaceutical sciences
  • 1 April 1994
The in vitro growth inhibitory activities of the ara-C derivatives against murine lymphocytic leukemia L1210 cells indicate that prodrug to drug conversion readily occurs and confirms previous findings about the versatility of the formamidine modification of nucleosides bearing exocyclic amino groups. Expand
Inhibition of thymidylate synthetase by showdomycin and its 5'-phosphate.
  • T. Kalman
  • Chemistry, Medicine
  • Biochemical and biophysical research…
  • 15 November 1972
Results suggest that the maleimide moiety of showdomycin alkylates a reactive sulfhydryl group at the active site of thymidylate synthetase, and are consistent with a sulfHydryl addition-elimination mechanism of the enzyme catalyzed reaction. Expand
Synthesis and biological activity of aromatic amino acid phosphoramidates of 5-fluoro-2'-deoxyuridine and 1-beta-arabinofuranosylcytosine: evidence of phosphoramidase activity.
It is proposed that the metabolism of theosphoramidate diesters of FUdR in proliferating tissue proceeds through two separate enzymatic steps involving P-N bond cleavage by an unknown phosphoramidase followed by P-O bond cleaving by phosphatases such as 5'-nucleotidase. Expand