Abstract
Synthetic 5'-amino-5'-deoxythymidine (5'-AdThd), α, β-methylenethymidine diphosphate (α, β-MTDP), and α, β-methylenethymidine triphosphate (α, β-MTTP) were found to inhibit thymidine kinase. Using thymidine kinase extracted from FM 3A/B cells (a strain of mouse mammary gland tumor cells), the Ki values of 5'-AdThd, α, β-MTDP, and α, β-MTTP against thymidine were calculated to be 9.2 × 10-5M, 2.3 × 10-5M, and 1.8 × 10-5M, respectively. At concentrations above their Ki values α, β-MTDP and α, β-MTTP did not inhibit incorporation of labeled thymidine into DNA of cultured cells, whereas 5'-AdThd did. Under the same conditions all three compounds inhibited TMP incorporation. The inhibitions of thymidine and TMP incorporation were specific, since the incorporation of deoxyguanosine was scarcely inhibited by 5'-AdThd. These results suggested that the specific inhibition of thymidine and TMP incorporation was mostly due to reduction in permeability of the cells to these substrates rather than to inhibition of thymidine kinase activity.
