A reappraisal of the effect upon thymidine kinase of thymidine derivatives carrying large groups at the 5'-position.
Several thymidine derivatives with hydrophobic 5'-substituents, linked by chemically stable amide and ether links, were synthesized as potential thymidine kinase inhibitors. None of these was active nor were several derivatives of thymidine 5'-acetate, which were previously reported to be inhibitors. It was shown that the apparent inhibition by the latter compounds was due to their facile hydrolysis in aqueous solution with release of thymidine. These results must cast doubt on any conclusions drawn from biological studies with 5'-esters of thymidine.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007939:Leukemia L1210 / Q000201:enzymology; D051379:Mice; D013936:Thymidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors*; D013938:Thymidine Monophosphate / Q000378:metabolism
D013938:Thymidine Monophosphate; D013937:Thymidine Kinase; D013936:Thymidine