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Applications[ edit ] Identification of dividing cells[ edit ] The first indirect use of thymidine kinase in biochemical research was the identification of dividing cells by incorporation of radiolabeled thymidine and subsequent measurement of the radioactivity or autoradiography to identify the dividing cells.
For this purpose tritiated thymidine is included in the growth medium.
PET scan of active tumors[ edit ] Fluorothymidine is a thymidine analog. Its uptake is regulated by thymidine kinase 1, and it is therefore taken up preferentially by rapidly proliferating tumor tissue.
The fluorine isotope 18 is a positron emitter that is used in positron emission tomography PET. The fluorine radiolabeled fluorothymidine F is therefore useful for PET imaging of active tumor proliferation, and compares favorably with the more commonly used marker fludeoxyglucose 18F. Hybridomas can be expanded to produce large quantities of immunoglobulins with a given unique specificity monoclonal antibodies.
One problem is to single out the hybridomas from the large excess of unfused cells after the cell fusion. After fusion, the cells are grown in a medium with methotrexate  or aminopterin  that inhibit the enzyme dihydrofolate reductase thus blocking the de novo synthesis of thymidine monophosphate.
One such medium that is commonly used is HAT medium, which contains hypoxanthine, aminopterinand thymidine.
The unfused cells from the thymidine kinase-deficient cell line die because they have no source of thymidine monophosphate. The lymphocytes eventually die because they are not "immortal. Those that produce the desired antibody are then selected and cultured to produce the monoclonal antibody.
Study of chromosome structure[ edit ] Molecular combing of DNA fibers can be used to monitor the structure of chromosomes in the budding yeast Saccharomyces cerevisiae.
This provides DNA replication profiles of individual molecules. This requires that the yeast strains express thymidine kinase, which wild type yeasts so not, being fungi see occurrence. Thymidine kinase in clinical chemistry Thymidine kinase is a salvage enzyme that is only present in anticipation of cell division.
The enzyme is not set free from cells undergoing normal division where the cells have a special mechanism to degrade the proteins no longer needed after the cell division.
Tumor cells release enzyme to the circulation, probably in connection with the disruption of dead or dying tumor cells. The thymidine kinase level in serum therefore serves as a measure of malignant proliferation, indirectly as a measure of the aggressivity of the tumor.
Therapeutic applications[ edit ] Some drugs are specifically directed against dividing cells. They can be used against tumors and viral diseases both against retrovirus and against other virusas the diseased cells replicate much more frequently than normal cells and also against some non-malignant diseases related to excessively rapid cell replication for instance psoriasis.
It has been suggested that the antiviral and anti-cancer activity of thymidine analogues is, at least partly, achieved by down-regulation of mitochondrial thymidine kinase.
The monophosphate is further phosphorylated to the corresponding triphosphate and incorporated in the growing DNA chain. J05AF04 it has been removed without replacement.
One common consequence of AIDS is lymphoma and the most important diagnostic application of thymidine kinase determination is for monitoring of lymphoma.
Chemical structures of thymidine kinase substrate analogs AZT.Publications. Matveenko, M., Cichero, E., Fossa, P., Becker, C.F. () Impaired Chaperone Activity of Human Heat Shock Protein Hsp27 Site-Specifically.
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Semisynthesis of human thymidine monophosphate kinase Protein semisynthesis based on native chemical ligation has become a major protein engineering tool that allows manipulation of domains of proteins of all sizes.
Access to integral membrane proteins via chemical synthesis or semisynthesis can provide detailed insights into the assembly and function of this diverse class of proteins.
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