Synthesis, crystal structure, and in vitro biological evaluation of C-6 pyrimidine derivatives: new lead structures for monitoring gene expression in vivo

…, Y Westermaier, R Perozzo, TG Kraljević…

Index: Martic, Miljen; Pernot, Lucile; Westermaier, Yvonne; Perozzo, Remo; Kraljevic, Tatjana Gazivoda; Kristafor, Svjetlana; Raic-Malic, Silvana; Scapozza, Leonardo; Ametamey, Simon Nucleosides, Nucleotides and Nucleic Acids, 2011 , vol. 30, # 4 p. 293 - 315

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Citation Number: 11

Abstract

Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1, 3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to “gold standard” 9-[4-fluoro-3-(hydroxymethyl) butyl] guanine, FHBG,(K m= 10±0.3 μM; k cat= 0.036±0.015 sec− 1). Additionally, it does ...