thymidine monophosphate function
After which, it is methylated by the enzyme thymidylate synthase to form thymidine. In the absence of oxygen, both compounds are consumed to yield a product in which the pterin moiety is covalently linked to the thymine. In addition to disease progression, both β2M and TKA have been associated with short duration of remission and inferior survival after treatment. Thus, because TK1 enzyme is highly dependent on the growth stage of the cell, the enzyme is a useful indicator for cellular proliferation and, hence, for malignancy (He et al., 1991; Sherley et al., 1988). A.M. Wu, in Advances in Immunology, 2016. Get the latest public health information from CDC: Although thymine is less reactive than purine nucleobases, our results showed that Ptr is able to photoinduce the degradation of dTMP and that the process is initiated by an electron transfer from the nucleotide to the triplet excited state of Ptr. Elevated thymidine kinase activity (TKA) has been observed to be predictive of early progression in a subgroup of untreated patients with smoldering CLL. Clipboard, Search History, and several other advanced features are temporarily unavailable. Zahra Karjoo, ... Arash Hatefi, in Gene Therapy of Cancer (Third Edition), 2014. For example, protein engineering techniques such as site-directed mutagenesis have been used to modify enzyme kinetics and divert enzyme affinity (Km) from its natural substrate to the prodrug [12]. The success of this case report led to an expanded trial (NCT01082926) but results are yet to be published on the efficacy. β2-Microglobulin (β2M) is an extracellular protein component of the human leukocyte antigen (HLA) class I complex. The lack of prior exposure to HSV may prevent mice from developing immunogenicity to this PET reporter making it useful as a preclinical tool. In addition, various nucleoside analogs used as antivirals, can be converted to the corresponding nucleoside monophosphates (322). We have investigated the ability of pterin (Ptr), the parent compound of oxidized pterins, to photosensitize the degradation of the pyrimidine nucleotide thymidine 5'-monophosphate (dTMP) in aqueous solutions under UV-A irradiation. We use cookies to help provide and enhance our service and tailor content and ads. Keywords: ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, Naoyuki Kamatani, ... André B.P. Herpes simplex virus thymidine kinase (HSVtk), the most commonly used TK gene for cancer gene therapy, was successfully delivered individually as well as in combination with ganciclovir (GCV) (a prodrug) in vivo. We have developed and characterized an anti-TK1 rabbit polyclonal antibody (He et al., 1996), two anti-TK1 monoclonal antibodies (Svanova Biotech, Sweden) raised against a 15 amino acid synthetic peptide (KPGEAVAARKLFAPQ), and an anti-TK1 chicken IgY antibody raised against a 31 amino acid synthetic peptide (GQPAG PDNKE NCPVP GKPGE AVAAR KLFAPQ), sequences corresponding to the part of the C-terminus of human TK1 (Wu et al., 2003). We have investigated the ability of pterin (Ptr), the parent compound of oxidized pterins, to photosensitize the degradation of the pyrimidine nucleotide thymidine 5'-monophosphate (dTMP) in aqueous solutions under UV-A irradiation. Uridine Monophosphate is found in cells of almost all living organisms, including bacteria. Its activity is highest in G1-S translation checkpoint and then declines rapidly in the G2 phase of the cell cycle. penciclovir has been modified to generate a radiolabeled analog 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine (FHBG) for use in high-quality PET imaging studies [43]. Under healthy physiological conditions, [18F]-FHBG does not cross (Yaghoubi et al., 2001). For instance, as shown by Alauddin et al. dTTP is also a metabolite that has been observed in … dTTP is one of the monomeric nucleotides that make up DNA. The success of HSVTK/GCV therapy in cancer relies on the bystander effect, which has been studied extensively both in vitro and in vivo. In DNA, dTTP complementary base pairs with dATP. Ganciclovir, which also acts as a chain terminator, is phosphorylated by a different enzyme and is used with some success. Normal cells will metabolize TFT to a toxic metabolite and will not be able to grow in its presence. Thymidylate kinase also known as deoxythymidylate kinase or dTMP kinase is an enzyme that in humans is encoded by the DTYMK gene. Biological functions . Intravitreal implants of ganciclovir have been used for the treatment of CMV retinitis. TK is an enzyme that catalyses the phosphorylation of deoxythymidine to deoxythymidine monophosphate. Some mutants, particularly dm30-tk and SR39-TK, have shown increased specificity for GCV [13,35,38–40]. Photosensitization; Pterins; Thymine; Type I photooxidation. HSV-TK was first given to patients clinically when expanded lymphocytes used to treat graft vs leukemia were engineered to express HSV-TK as a suicide gene. A phase II clinical trial is ongoing to investigate the suitability of [18F] FHBG in breast cancer, glioma, and central nervous system (CNS) neoplasms (, identifier NCT00185848). M.N. Tchounwou, in Brenner's Encyclopedia of Genetics (Second Edition), 2013. β2M has been shown to have significant prognostic relevance in lymphoma and multiple myeloma patients and correlates with disease burden in CLL patients. P.B. Conversion of prodrug GCV into the active form by the expressed HSVtk promoted the bystander effects responsible for killing surrounding untransducted tumor cells.  |  This makes penciclovir a better alternative to ganciclovir because it prevents neoplasia induced by chromosomal damage and rearrangements [44]. Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide.AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine; it is an ester of phosphoric acid and the nucleoside adenosine. This site needs JavaScript to work properly. Thymidine kinase (TK, ATP: thymidine 5′-phosphotransferase, EC., an enzyme of the pyrimidine salvage pathway, catalyzes the phosphorylation of thymidine to thymidine monophosphate. In a similar approach, repeated delivery of HSVtk gene using hemagglutinating virus of Japan (HVJ)-liposomes in the induced liver tumors, followed by GCV treatment significantly inhibited the tumor growth and markedly improving the survival of animals. For example, whereas penciclovir, an ester analog of ganciclovir, and ganciclovir could both trigger apoptosis in HSVTK-expressing Chinese hamster ovary cells, penciclovir had reduced genotoxic effect and led to fewer chromosomal aberrations and recombination events. Copyright © 2016 Elsevier Inc. All rights reserved. These antibodies are useful for probe in both serologic and immunohistochemic detection of TK1 in patients of all types of cancer diseases (He et al., 2000; Kuroiwa et al., 2001; Mao et al., 2002; Wang et al., 2001; Wu et al., 2000, 2003; Zhang et al., 2001; Zou et al., 2002).


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