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  • nucleosides
  • We report here the cloning and in-depth characterization of one T. brucei brucei ENT member, TbNT9/AT-D. This transporter was expressed in Saccharomyces cerevisiae and displayed a uniquely high affinity for adenosine ( K m = 0.068 ± 0.013 μM), as well as broader selectivity for other purine nucleosides in the low micromolar range, but was not inhibited by nucleobases or pyrimidines. (aspetjournals.org)
  • In addition, we show that the 6-position amine group of adenosine, but not the inosine 6-keto group, makes a major contribution to binding (ΔG 0 = 12 kJ/mol), explaining the different K m values of the purine nucleosides. (aspetjournals.org)
  • Therefore, we propose that addition of ABCG2 inhibitors would effectively increase the antitumor efficacy of purine nucleosides by blocking drug efflux that may be a significant mode of resistance when dCK levels are low. (aacrjournals.org)
  • Notably recent studies have shown that the ABC transporter ABCG2 [which is expressed in many tumor types ( 22 )] exports both purine nucleoside monophosphates and nucleosides ( 18 , 23 ).This suggests an ABC transporter could affect the intracellular nucleoside monophosphate concentration by reducing both the amount of nucleoside available for phosphorylation as well as the amount phosphorylated. (aacrjournals.org)
  • The finding that ABCG2 mediates the efflux of both purine nucleosides and nucleoside monophosphates ( 18 , 23 ) and the fact that some nucleoside analogues are good dCK substrates ( 11 ) suggested that intracellular dCK activity might affect ABCG2-mediated drug export ( Fig. 1A ). (aacrjournals.org)