Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two forms of deoxythymidine kinase from blast cells of acute myelocytic leukemia were identified by electrophoresis. One was associated mainly with the cytoplasm and the other with mitochondria. Both isozymes were separated and purified by differential affinity column chromatography which resulted in 2416- and 1634-fold purification of the cytoplasmic and mitochondrial enzymes, respectively. Affinity gel was prepared by linkage through position 3' of deoxythymidine. Each enzyme had the same electrophoretic mobility in the purified state as it did in the enzyme derived from the corresponding subcellular fraction of the homogenate. Thymidine phosphorylase was not retarded by the affinity column. The purified cytoplasmic and mitochondrial deoxythymidine kinase had different molecular weights, sensitivities to inhibition by ammonium sulfate, activation energies for the reaction and divalent cation requirements. Adenosine, guanosine, and cytosine 3':5'-monophosphates, putrescine, spermine, and spermidine were neither activators nor inhibitors of either deoxythymidine kinase.
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PMID:Human deoxythymidine kinase. I. Purification and general properties of the cytoplasmic and mitochondrial isozymes derived from blast cells of acute myelocytic leukemia. 106 25

P1-(Adenosine-5')-Pn-(thymidine-5') tri-, tetra-, penta-, and hexaphosphates (ApnT) plus the analogues with a methylene group alpha, beta to the thymidine residue (ApncpT) were synthesized by coupling the appropriate two nucleotides, having activated one by morpholine. These were tested as potential dinucleotide inhibitors of thymidine kinase, thymidylate kinase, and ribonucleotide reductase. All three enzymes bind ATP and thymidine or its nucleotides and therefore might be inhibited by dinucleotides containing adenosine and thymidine. Ap5T and Ap6T strongly inhibited all three enzymes (IC50 = 2.4-20 microM). Ap4cpT and Ap5cpT also strongly inhibited the two kinases (IC50 = 4-20 microM) but were much weaker inhibitors of the reductase (IC50 = 130 and 230 microM).
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PMID:Dinucleotide analogues as inhibitors of thymidine kinase, thymidylate kinase, and ribonucleotide reductase. 283 31