thymidine monophosphate


Summary: 5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety.

Top Publications

  1. Ferraro P, Nicolosi L, Bernardi P, Reichard P, Bianchi V. Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate. Proc Natl Acad Sci U S A. 2006;103:18586-91 pubmed
    ..At nM external dTMP the nucleotide is concentrated 100-fold inside the mt matrix. Export of thymidine phosphates was much slower and possibly occurred at the level of dTDP. ..
  2. Uckun F, Petkevich A, Vassilev A, Tibbles H, Titov L. Stampidine prevents mortality in an experimental mouse model of viral hemorrhagic fever caused by lassa virus. BMC Infect Dis. 2004;4:1 pubmed
  3. Myllykallio H, Lipowski G, Leduc D, Filee J, Forterre P, Liebl U. An alternative flavin-dependent mechanism for thymidylate synthesis. Science. 2002;297:105-7 pubmed publisher
    ..Our findings reveal complexity in the evolution of thymidine in present-day DNA. Because ThyX proteins are found in many pathogenic microbes, they present a previously uncharacterized target for antimicrobial compounds...
  4. Uckun F, Pendergrass S, Venkatachalam T, Qazi S, Richman D. Stampidine is a potent inhibitor of Zidovudine- and nucleoside analog reverse transcriptase inhibitor-resistant primary clinical human immunodeficiency virus type 1 isolates with thymidine analog mutations. Antimicrob Agents Chemother. 2002;46:3613-6 pubmed
  5. Uckun F, Chen C, Lisowski E, Mitcheltree G, Venkatachalam T, Erbeck D, et al. Toxicity and pharmacokinetics of stampidine in mice and rats. Arzneimittelforschung. 2003;53:357-67 pubmed
    ..administration of the nontoxic 25-50 mg/kg bolus doses of stampidine. The remarkable in vivo safety of stampidine warrants the further development of this promising new antiviral agent for possible clinical use in HIV-infected patients. ..
  6. Van Poecke S, Munier Lehmann H, Helynck O, Froeyen M, Van Calenbergh S. Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase. Bioorg Med Chem. 2011;19:7603-11 pubmed publisher
    We report on Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitory activities of a series of new 3'- and 5'-modified thymidine analogues including ?- and ?-derivatives...
  7. Kumar A, Sevilla M. Low-energy electron attachment to 5'-thymidine monophosphate: modeling single strand breaks through dissociative electron attachment. J Phys Chem B. 2007;111:5464-74 pubmed
    ..e., the nucleotide, 5'-thymidine monophosphate (5'-dTMPH)...
  8. Gattis S, Palfey B. Direct observation of the participation of flavin in product formation by thyX-encoded thymidylate synthase. J Am Chem Soc. 2005;127:832-3 pubmed
    ..The formation of inactivated enzyme without flavin oxidation indicates that methylene transfer from the folate to the nucleotide occurs prior to flavin redox chemistry. ..
  9. Leduc D, Graziani S, Meslet Cladiere L, Sodolescu A, Liebl U, Myllykallio H. Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea. Biochem Soc Trans. 2004;32:231-5 pubmed
    ..In this contribution, we discuss the differences in the distinct mechanisms of dTMP synthesis, with a special emphasis on hyperthermophilic micro-organisms. ..

More Information


  1. Sotelo Mundo R, Changchien L, Maley F, Montfort W. Crystal structures of thymidylate synthase mutant R166Q: structural basis for the nearly complete loss of catalytic activity. J Biochem Mol Toxicol. 2006;20:88-92 pubmed
    ..synthase (TS) catalyzes the folate-dependent methylation of deoxyuridine monophosphate (dUMP) to form thymidine monophosphate (dTMP)...
  2. Rode W, Dabrowska M, Zielinski Z, Gołos B, Wranicz M, Felczak K, et al. Trichinella spiralis and Trichinella pseudospiralis: developmental patterns of enzymes involved in thymidylate biosynthesis and pyrimidine salvage. Parasitology. 2000;120 ( Pt 6):593-600 pubmed
    ..A hypothesis is discussed, assuming high expression of thymidylate synthase in muscle larvae to be connected with their cells being arrested in the cell cycle. ..
  3. Scotti M, Stella L, Shearer E, Stover P. Modeling cellular compartmentation in one-carbon metabolism. Wiley Interdiscip Rev Syst Biol Med. 2013;5:343-65 pubmed publisher
  4. Wiersma Koch H, Sunden F, Herschlag D. Site-directed mutagenesis maps interactions that enhance cognate and limit promiscuous catalysis by an alkaline phosphatase superfamily phosphodiesterase. Biochemistry. 2013;52:9167-76 pubmed publisher
  5. Das S, Fujimura R. Processiveness of DNA polymerases. A comparative study using a simple procedure. J Biol Chem. 1979;254:1227-32 pubmed
    ..With "nicked DNA-like" poly(dA):oligo(dT), the processiveness of E. coli DNA polymerase I is increased 2- to 2.5-fold. The significance of this increase in determining the "patch size" during DNA repair is discussed. ..
  6. Uckun F, Tai H, D Cruz O. Antileukemic activity and cellular metabolism of the aryl phosphate derivative of bromo-methoxy zidovudine (compound WHI-07). Arzneimittelforschung. 2005;55:50-65 pubmed
  7. Doucet N, Jayasundera T, Simonovic M, Loria J. The crystal structure of ribonuclease A in complex with thymidine-3'-monophosphate provides further insight into ligand binding. Proteins. 2010;78:2459-68 pubmed publisher
    ..Accumulating evidence suggests that very subtle structural, chemical, and potentially motional variations contribute to ligand discrimination in this enzyme. ..
  8. Cassano A, Anderson V, Harris M. Evidence for direct attack by hydroxide in phosphodiester hydrolysis. J Am Chem Soc. 2002;124:10964-5 pubmed
    ..027 +/- 0.010. This large kinetic component suggests that little bond order to the nucleophile occurs in the transition state. ..
  9. Sugaya Y, Ihara K, Masuda Y, Ohtsubo E, Maki H. Hyper-processive and slower DNA chain elongation catalysed by DNA polymerase III holoenzyme purified from the dnaE173 mutator mutant of Escherichia coli. Genes Cells. 2002;7:385-99 pubmed
    ..A link between the proofreading and chain elongation processes was suggested. ..
  10. Lévesque S, Lavoie E, Lecka J, Bigonnesse F, Sevigny J. Specificity of the ecto-ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases. Br J Pharmacol. 2007;152:141-50 pubmed
    ..In addition, ARL 67156 is not an effective inhibitor of NTPDase2, human NTPDase8, NPP3 and ecto-5'-nucleotidase. ..
  11. Cheng T, Rey P, Poon T, Kan C. Kinetic studies of human tyrosyl-DNA phosphodiesterase, an enzyme in the topoisomerase I DNA repair pathway. Eur J Biochem. 2002;269:3697-704 pubmed
    ..Purified recombinant human TDPNDelta39 cleaved p-nitrophenyl-thymidine-3'-phosphate with Km and kcat values of 211.14 +/- 23.83 micro m and 8.82 +/- 0.57 per min in the presence of Mn2+. ..
  12. McIntosh E, Haynes R. Isolation of a Saccharomyces cerevisiae mutant strain deficient in deoxycytidylate deaminase activity and partial characterization of the enzyme. J Bacteriol. 1984;158:644-9 pubmed
    ..The auxotrophic requirement of dcd1 dmp1 tup7 strains also can be satisfied by exogenous dTMP but not deoxyuridine. ..
  13. Arjmand F, Muddassir M. Design and synthesis of heterobimetallic topoisomerase I and II inhibitor complexes: in vitro DNA binding, interaction with 5'-GMP and 5'-TMP and cleavage studies. J Photochem Photobiol B. 2010;101:37-46 pubmed publisher
    ..In addition, the complexes show high inhibition activity against topoisomerase I and II. However, complex 4 exhibits significant inhibitory effects on the Topo I activity at a very low concentration approximately 2.5 microM. ..
  14. Pontarin G, Ferraro P, Valentino M, Hirano M, Reichard P, Bianchi V. Mitochondrial DNA depletion and thymidine phosphate pool dynamics in a cellular model of mitochondrial neurogastrointestinal encephalomyopathy. J Biol Chem. 2006;281:22720-8 pubmed
    ..Thus MNGIE patients may increase their consumption of ATP to counteract an unlimited expansion of the dTTP pool caused by circulating thymidine...
  15. Adhikari S, Karmahapatra S, Elias H, Dhopeshwarkar P, Williams R, Byers S, et al. Development of a novel assay for human tyrosyl DNA phosphodiesterase 2. Anal Biochem. 2011;416:112-6 pubmed publisher
    ..Our results suggest that this novel assay system with this new TDP2 substrate can be used for inhibitor screening in a high-throughput manner. ..
  16. Modrzejewska H, Brzezinska E, Dramiński M, Zgit Wróblewska A, Krzykowska K, Rozpończyk E, et al. A study of the influence of newly synthesized acyclonucleosides and 1,2,3,4-tetrahydroisoquinoline derivatives on deoxythymidine and deoxycytidine kinase activities in human neurofibrosarcoma and ovarian cancer. Acta Biochim Pol. 2003;50:1175-85 pubmed
    ..9% of incorporation inhibition) into tumour DNA. The obtained results point to the mechanism of uracil acyclonucleosides and 1,2,3,4-tetrahydroisoquinoline biological activity consisting in inhibiting the synthesis of DNA components...
  17. Furstenau C, Trentin D, Barreto Chaves M, Sarkis J. Ecto-nucleotide pyrophosphatase/phosphodiesterase as part of a multiple system for nucleotide hydrolysis by platelets from rats: kinetic characterization and biochemical properties. Platelets. 2006;17:84-91 pubmed
    ..Using p-nitrophenyl 5'-thymidine monophosphate (p-Nph-5'-TMP) as a substrate for E-NPP, we demonstrate an enzyme activity that shares the major ..
  18. Lee L, Cheng Y. Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia. J Biol Chem. 1977;252:5686-91 pubmed
    ..dTMP was the only preferred phosphate receptor among all the monophosphate nucleotides tested dTTP and IdUTP competed with both substrates and inhibited the reaction with a Ki of 0.75 mM and 1.1 mM, respectively. ..
  19. Venkatachalam T, Qazi S, Uckun F. Site-specific enzymatic activation of the anti-HIV agent stampidine. Arzneimittelforschung. 2006;56:167-75 pubmed
    ..Enzymes such as lipase, esterase and protease did not hydrolyze the butyl substituted STAMP analog. These experimental results show that the site of attack for the enzymatic hydrolysis of STAMP is the ester side chain of the molecule. ..
  20. Eliahu S, Lecka J, Reiser G, Haas M, Bigonnesse F, Lévesque S, et al. Diadenosine 5',5''-(boranated)polyphosphonate analogues as selective nucleotide pyrophosphatase/phosphodiesterase inhibitors. J Med Chem. 2010;53:8485-97 pubmed publisher
    ..Our data provide strong evidence that analogue 2 is the first specific NPP inhibitor to be described. ..
  21. Swarts S, Sevilla M. Radiolysis of spin-labeled DNA: an electron spin resonance investigation. Radiat Res. 1987;112:21-35 pubmed
    ..In the presence of oxygen, there is a dramatic decrease in the loss of both the free and DNA-bound probes due to the lack of reaction of these probes with peroxyl radicals formed by the addition of molecular oxygen to DNA radicals. ..
  22. Sorokin V, Valeev V, Gladchenko G, Sysa I, Blagoi Y, Volchok I. Interaction of bivalent copper, nickel, manganese ions with native DNA and its monomers. J Inorg Biochem. 1996;63:79-98 pubmed
    ..No transformations of this kind of helix-coil transitions are caused by manganese and nickel up to concentrations 4 X 10(-2) M. ..
  23. Weiss B. The deoxycytidine pathway for thymidylate synthesis in Escherichia coli. J Bacteriol. 2007;189:7922-6 pubmed
    ..The pathway requires the gene for any of three nucleoside diphosphate kinases (ndk, pykA, or pykF) and the gene for a 5'-nucleotidase (yfbR). ..
  24. Venkatachalam T, Qazi S, Uckun F. Synthesis, separation and anti-HIV activity of distereoisomers of N-[p-(4-bromophenyl) -2',3'-didehydro-3'-deoxy-5'-thymidylyl]-L-alanine methyl ester (stampidine). Arzneimittelforschung. 2006;56:152-8 pubmed
    ..Both isomers were active against the HIV-1 strain HTLV(IIIB) and neither isomer was more or less active than distereoisomeric mixture of stampidine. ..
  25. Leduc D, Escartin F, Nijhout H, Reed M, Liebl U, Skouloubris S, et al. Flavin-dependent thymidylate synthase ThyX activity: implications for the folate cycle in bacteria. J Bacteriol. 2007;189:8537-45 pubmed
    ..In addition, our observations suggest that the presence of flavin-dependent thymidylate synthase X provides growth benefits under conditions in which the level of reduced folate derivatives is compromised. ..
  26. D Cruz O, Venkatachalam T, Uckun F. Structural requirements for potent human spermicidal activity of dual-function aryl phosphate derivative of bromo-methoxy zidovudine (compound WHI-07). Biol Reprod. 2000;62:37-44 pubmed
    ..WHI-07 and its Trp analogues hold particular clinical promise for the development of novel, nondetergent-type prophylactic contraceptives for the prevention of heterosexual HIV/acquired immunodeficiency syndrome transmission. ..
  27. Jing C, Cornish V. A fluorogenic TMP-tag for high signal-to-background intracellular live cell imaging. ACS Chem Biol. 2013;8:1704-12 pubmed publisher
  28. Venkatachalam T, Samuel P, Qazi S, Uckun F. Effect of change in nucleoside structure on the activation and antiviral activity of phosphoramidate derivatives. Bioorg Med Chem. 2005;13:5408-23 pubmed
  29. Rampazzo C, Gallinaro L, Milanesi E, Frigimelica E, Reichard P, Bianchi V. A deoxyribonucleotidase in mitochondria: involvement in regulation of dNTP pools and possible link to genetic disease. Proc Natl Acad Sci U S A. 2000;97:8239-44 pubmed
    ..We localized the gene for dNT-2 on chromosome 17p11.2 in the Smith-Magenis syndrome-critical region, raising the possibility that dNT-2 is involved in the etiology of this genetic disease. ..
  30. Gu J, Xie Y, Schaefer H. Electron attachment to nucleotides in aqueous solution. Chemphyschem. 2006;7:1885-7 pubmed
  31. Yang S, Pannecouque C, Herdewijn P. Synthesis, and in vitro enzymatic and antiviral evaluation of d4T polyphosphate derivatives as chain terminators. Chem Biodivers. 2012;9:2186-94 pubmed publisher
    ..The data suggests that these d4T polyphosphate derivatives are hydrolyzed to d4T and rephosphorylated to d4TTP before exerting their antiviral activity. ..
  32. Hildenbrand K. The SO4-.-induced oxidation of 2'-deoxyuridine-5'-phosphate, uridine-5'-phosphate and thymidine-5'-phosphate. An ESR study in aqueous solution. Z Naturforsch C. 1990;45:47-58 pubmed
    ..In 5'-UMP transfer of the radical site from the base to the sugar moiety competes with intramolecular phosphate addition. ..
  33. Campbell M, Miller P. Phosphodiester-mediated reaction of cisplatin with guanine in oligodeoxyribonucleotides. Biochemistry. 2008;47:12931-8 pubmed publisher
    ..These observations suggest that interactions between cisplatin and the negatively charged phosphodiester backbone may play an important role in facilitating platination of guanine nucleotides in DNA. ..
  34. D Cruz O, Uckun F. Microbicides for multidrug-resistant and multitropic HIV-1. Curr Opin Investig Drugs. 2008;9:152-69 pubmed
    ..Extensive preclinical studies have shown that stampidine and a candidate thiourea NNRTI (HI-443) have clinical potential as a safe combination microbicide to inhibit, prevent or treat mucosal HIV-1 infections. ..
  35. Birk A, Bubman D, Broekman M, Robertson H, Drosopoulos J, Marcus A, et al. Role of a novel soluble nucleotide phospho-hydrolase from sheep plasma in inhibition of platelet reactivity: hemostasis, thrombosis, and vascular biology. J Lab Clin Med. 2002;139:116-24 pubmed
    ..A specific phosphodiesterase substrate, p -nitrophenol-5'-thymidine monophosphate (TMP) (p -Nph-5'-TMP), was readily hydrolyzed in sheep plasma at a rate of approximately 0...
  36. Yutani M, Ogita A, Fujita K, Usuki Y, Tanaka T. Evaluation of uridine 5'-eicosylphosphate as a stimulant of cyclic AMP-dependent cellular function. Gen Physiol Biophys. 2011;30:106-9 pubmed publisher
    ..We suppose the inhibitory effect of UMPC20 could indeed reflect the elevation of the cellular cAMP level. ..
  37. Silber J, Le Menn A, Chevillard S, Zider A, Paumard S. The vestigial locus of Drosophila melanogaster is involved in resistance to inhibitors of dTMP synthesis. Mol Gen Genet. 1993;241:42-8 pubmed
    ..Our results indicate a role for the vestigial locus in mediating resistance to inhibitors of dTMP synthesis. ..
  38. Kalek M, Madsen A, Wengel J. Effective modulation of DNA duplex stability by reversible transition metal complex formation in the minor groove. J Am Chem Soc. 2007;129:9392-400 pubmed
    ..Alternating addition of metal ions and EDTA demonstrated reversibility of metal ion-induced changes in hybridization strength, proving that the described approach provides an efficient method for duplex stability modulation. ..
  39. Hoes I, Lemiere F, Van Dongen W, Vanhoutte K, Esmans E, Van Bockstaele D, et al. Analysis of melphalan adducts of 2'-deoxynucleotides in calf thymus DNA hydrolysates by capillary high-performance liquid chromatography-electrospray tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 1999;736:43-59 pubmed
    ..In the case of 2'-deoxyadenosine monophosphate, thymidine monophosphate and 2'-deoxyguanosine phosphate alkylation was observed in the mononucleotide reaction mixtures but not ..
  40. Müller H, Meier C, Balzarini J, Reinstein J. Novel nucleotide analogues as potential substrates for TMPK, a key enzyme in the metabolism of AZT. Nucleosides Nucleotides Nucleic Acids. 2003;22:821-3 pubmed
    ..Investigation of the substrate properties of the modified nucleotides towards TmpK showed, that they are very poor substrates for this key enzyme in the bioactivation of AZT. ..
  41. Marzano C, Severin E, Bordin F. Can a mixed damage interfere with DNA-protein cross-links repair?. J Cell Mol Med. 2001;5:171-7 pubmed
    ..TMP and 8-MOP induced chromosomal aberrations in CHO cells to the same extent, while FQ appeared to be more active. Our data suggest that the ISC induced by TMP could trap enzymes involved in DPC repair. ..
  42. Shoichet B, Leach A, Kuntz I. Ligand solvation in molecular docking. Proteins. 1999;34:4-16 pubmed
    ..Correcting for ligand solvation improved the rankings of known ligands and discriminated against molecules with inappropriate charge states and sizes. ..
  43. Fude F, Jin Z, Haixin L, Mingjia T. Study on GMA-DNA adducts. Chin Med Sci J. 1999;14:1-6 pubmed
    ..Formation of GMA-DNA adducts is an important molecular event in gene mutation and cell transformation induced by GMA. ..
  44. Ostermann N, Segura Peña D, Meier C, Veit T, Monnerjahn C, Konrad M, et al. Structures of human thymidylate kinase in complex with prodrugs: implications for the structure-based design of novel compounds. Biochemistry. 2003;42:2568-77 pubmed
    ..the determinants for efficient conversion by the enzyme thymidylate kinase (TMPK) of clinically important thymidine monophosphate analogues to the corresponding diphosphates, we solved the crystal structures of the enzyme, with either ..
  45. Sengle G, Eisenführ A, Arora P, Nowick J, Famulok M. Novel RNA catalysts for the Michael reaction. Chem Biol. 2001;8:459-73 pubmed
    ..Therefore, previously unforeseen RNA-evolution pathways can be considered, for example the formation of dTMP from dUMP. The substrate specificity of this ribozyme may also render it useful in organic syntheses. ..
  46. Guo M, Guo Z, Sadler P. Titanium(IV) targets phosphoesters on nucleotides: implications for the mechanism of action of the anticancer drug titanocene dichloride. J Biol Inorg Chem. 2001;6:698-707 pubmed
    ..The high affinity of Ti(IV) for phosphate groups may be important for its biological activity. ..
  47. Ikeda K, Nagao Y, Achiwa K. Synthesis of sialic acid-containing nucleotide sugars: CMP-sialic acid analogs. Carbohydr Res. 1992;224:123-31 pubmed
  48. Mehellou Y, McGuigan C, Brancale A, Balzarini J. Design, synthesis, and anti-HIV activity of 2',3'-didehydro-2',3'-dideoxyuridine (d4U), 2',3'-dideoxyuridine (ddU) phosphoramidate 'ProTide' derivatives. Bioorg Med Chem Lett. 2007;17:3666-9 pubmed
    ..The findings from the modeling studies provide compelling evidence for the lack of anti-HIV activity of d4U phosphoramidates, in contrast with the corresponding ddU phosphoramidates. ..
  49. Lusic H, Uprety R, Deiters A. Improved synthesis of the two-photon caging group 3-nitro-2-ethyldibenzofuran and its application to a caged thymidine phosphoramidite. Org Lett. 2010;12:916-9 pubmed publisher
    ..Furthermore, its installation on a thymidine phosphoramidite is described. This caging group is efficiently removed through light-irradiation at 365 nm. ..
  50. Gadsden M, McIntosh E, Game J, Wilson P, Haynes R. dUTP pyrophosphatase is an essential enzyme in Saccharomyces cerevisiae. EMBO J. 1993;12:4425-31 pubmed
    ..These results are in general agreement with previous models in thymine-less death that implicate dUTP metabolism. They also suggest an alternative approach for chemotherapeutic drug design. ..
  51. Uckun F, Cahn P, Qazi S, D CRUZ O. Stampidine as a promising antiretroviral drug candidate for pre-exposure prophylaxis against sexually transmitted HIV/AIDS. Expert Opin Investig Drugs. 2012;21:489-500 pubmed publisher
    ..The discovery of stampidine as a potent antiretroviral agent represents a significant step forward in the development of effective therapeutic as well as preventive strategies against HIV/AIDS. ..
  52. Kato A, Yasuda Y, Kitamura Y, Kandeel M, Kitade Y. Carbocyclic thymidine derivatives efficiently inhibit Plasmodium falciparum thymidylate kinase (PfTMK). Parasitol Int. 2012;61:501-3 pubmed publisher
    ..The K(i)(dTMP) and K(i)(dGMP) values were 20 and 7 ?M respectively. Thus, further modifications of carbocyclic thymidine analogs represent a good strategy for developing more powerful thymidylate kinase inhibitors. ..
  53. MacFarlane A, McEntee M, Stover P. Azoxymethane-induced colon carcinogenesis in mice occurs independently of de novo thymidylate synthesis capacity. J Nutr. 2014;144:419-24 pubmed publisher
    ..Furthermore, enrichment of SHMT1 in the cytoplasm, as observed in Shmt1(tg+) mice, protects against AOM-mediated carcinogenesis independent of its role in nuclear de novo dTMP biosynthesis. ..