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Nonpolar nucleoside mimics as active substrates for human thymidine kinases

SK Jarchow-Choy, E Sjuvarsson…

文献索引:Jarchow-Choy, Sarah K.; Sjuvarsson, Elena; Sintim, Herman O.; Eriksson, Staffan; Kool, Eric T. Journal of the American Chemical Society, 2009 , vol. 131, p. 5488 - 5494

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被引用次数: 20

摘要

We describe the use of nonpolar nucleoside analogues of systematically varied size and shape to probe the mechanisms by which the two human thymidine kinases (TK1 and TK2) recognize and phosphorylate their substrate, thymidine. Comparison of polar thymidine with a nonpolar isostere, 2, 4-difluorotoluene deoxyriboside, as substrates for the two enzymes establishes that TK1 requires electrostatic complementarity to recognize the thymine base ...