Abstract
Thymidylate kinase (TMPK) is a key enzyme for pyrimidine synthesis that catalyzes the phosphorylation of thymidine 5’-monophosphate (dTMP) in the presence of ATP and Mg2+ to form thymidine 5’-diphosphate (dTDP), which is then converted to thymidine 5’-triphosphate (dTTP) by nucleoside-diphosphate kinase (NDK). TMPK has an important function in cell proliferation and its enzyme kinetics and related structures have been determined in various organisms. TMPK is well recognized as a potential drug target, with the most notable function being in the activation of anti-HIV nucleoside prodrugs. Recent studies have shown that TMPK is a validated target for antibiotic development against grampositive bacterium of Staphylococcus aureus. In addition, inhibition of human TMPK increases the potential of anticancer agent doxorubicin toward colon cancer cells regardless of p53 status. Following the rapid expanding knowledge on TMPKs and the rising interests in TMPKs as a drug target, in this review we try to describe current research on TMPKs in various organisms of eukaryotes, prokaryotes and viruses and to provide information for designing new potential inhibitors against TMPKs.
Keywords: AZTMP, cancer chemotherapy, infectious disease, thymidylate kinase, TMPK assay, TMPK inhibitor
Current Medicinal Chemistry
Title:Thymidylate Kinase: An Old Topic Brings New Perspectives
Volume: 20 Issue: 10
Author(s): Q. Cui, W. S. Shin, Y. Luo, J. Tian, H. Cui and D. Yin
Affiliation:
Keywords: AZTMP, cancer chemotherapy, infectious disease, thymidylate kinase, TMPK assay, TMPK inhibitor
Abstract: Thymidylate kinase (TMPK) is a key enzyme for pyrimidine synthesis that catalyzes the phosphorylation of thymidine 5’-monophosphate (dTMP) in the presence of ATP and Mg2+ to form thymidine 5’-diphosphate (dTDP), which is then converted to thymidine 5’-triphosphate (dTTP) by nucleoside-diphosphate kinase (NDK). TMPK has an important function in cell proliferation and its enzyme kinetics and related structures have been determined in various organisms. TMPK is well recognized as a potential drug target, with the most notable function being in the activation of anti-HIV nucleoside prodrugs. Recent studies have shown that TMPK is a validated target for antibiotic development against grampositive bacterium of Staphylococcus aureus. In addition, inhibition of human TMPK increases the potential of anticancer agent doxorubicin toward colon cancer cells regardless of p53 status. Following the rapid expanding knowledge on TMPKs and the rising interests in TMPKs as a drug target, in this review we try to describe current research on TMPKs in various organisms of eukaryotes, prokaryotes and viruses and to provide information for designing new potential inhibitors against TMPKs.
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Cite this article as:
Cui Q., S. Shin W., Luo Y., Tian J., Cui H. and Yin D., Thymidylate Kinase: An Old Topic Brings New Perspectives, Current Medicinal Chemistry 2013; 20 (10) . https://dx.doi.org/10.2174/0929867311320100006
DOI https://dx.doi.org/10.2174/0929867311320100006 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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