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

Syntheses are described of p1-(adenosine-5')-p3-(glucose-6) triphosphate (Ap3 glucose), Ap4 glucose, and p1-(adenosine-5')-P3-(thymidine-5') triphosphate (Ap3T). The compounds were not substrates of any of the enzymes used in the present studies. Ap3 glucose and Ap4 glucose were inhibitors of yeast hexokinase (HK) and the rat isozymes HK I-III; in general, they had less affinity for the enzymes than the substrates ATP and glucose. Inhibition constants (Ki values) of Ap3T with rat mitochondrial thymidine kinase (M-TK) and rat cytoplasmic TK (C-TK) were determined for variable thymidine (TdR) with a constant saturating level of ATP and for variable ATP with constant saturating TdR. Ap3T was a potent and selective inhibitor of M-TK [KM (TdR)/Ki = 1.6, KM (ATP)/Ki = 38 with variable ATP; KM (TdR) Ki = 0.06, KM (ATP)/Ki = 1.4 with variable TdR] relative to C-TK [KM (TdR)/Ki = 0.006, KM (ATP)/Ki = 0.7 with variable ATP; KM (TdR)/Ki = 0.001, KM (ATP)/Ki = 0.12 with variable TdR]. Inhibition of M-TK and C-TK by Ap3T differed qualitatively and quantitatively from inhibition under the same conditions by the metabolic feedback inhibitor TdR 5'-triphosphate.
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PMID:Species- or isozyme-specific enzyme inhibitors. 6. Synthesis and evaluation of two-substrate condensation products as inhibitors of hexokinases and thymidine kinases. 710 96

In our previous studies, we constructed the Bifidobacterium infantis thymidine kinase/nucleoside analogue ganciclovir (BI-TK/GCV) system, which was proven to have a sustainable antitumor activity in an in vivo bladder cancer rodent model. In this article, a proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ) and followed by liquid chromatography-tandem mass spectrometry was used to understand the molecular mechanisms of this system. iTRAQ identified 192 downregulated and 210 upregulated proteins after treatment with BI-TK/GCV in Sprague-Dawley rats. Downregulations of proliferating cell nuclear antigen (PCNA), pyruvate kinase isozymes M2 (PKM2), hexokinase 1 (HXK-1), 6-phosphofructokinase (PFK-B), and cell surface glycoprotein (CD146) in bladder cancer after treatment were confirmed by Western blot analysis and validated by immunohistochemistry. Furthermore, the networks of cancer proliferation associated with PCNA, glycolysis associated with PKM2, HXK-1, and PFK-B, and invasion associated with CD146 were illustrated using Ingenuity Pathway Analysis. This study represents the successful application of iTRAQ technology to reveal the molecular mechanisms of BI-TK/GCV treatment system and provides the theoretical support for the effectiveness of our successful treatment system.
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PMID:Proteomic analysis of bladder cancer by iTRAQ after Bifidobacterium infantis-mediated HSV-TK/GCV suicide gene treatment. 2389 87