SYNTHESIS OF STABLE ISOTOPE LABELED NUCLEOTIDES

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The SIR provided I -Te-Met; . 1 OOg The Te-Met was an alternate substrate for the enzyme S-adenosylmethionine (AdoMet) synthetase (ATP: L-methionine S-adenosyltransferase) which catalyzes the synthesis of the primary biological methylating agent, AdoMet. The reaction yields Te-adenosyltelluromethionine (Te-AdoMet) as confirmed by identification of a novel compound with the expected chromatographic properties. The reaction was quite facile with a Vmax of ca. 25% of the reaction with the natural substrate methionine and a Kni of 0.5 mM, only 6 fold larger than the Kni for methionine. If this reaction of Te-Met occurs in cells, it could affect many methylation reactions by altering the intracellular AdoMet pools, which could have large effects on metabolism and gene regulation. Our studies did not investigate in vivo effects of the Te-met. We are following our experimental studies with theoretical investigations of the effects of Tellurium replacement of Sulfur on hydrogen bonding and electrostatic interactions that might occur in a variety of biological settings.