Nonpolar nucleoside mimics as active substrates for human thymidine kinases

SK Jarchow-Choy, E Sjuvarsson…

Index: 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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Citation Number: 20

Abstract

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 ...