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   1  dihydropyrimidine dehydrogenase and targets thymidylate synthase.                                   
     2 e signaling molecules that can down-regulate thymidylate synthase.                                   
     3 ct as rTS signaling mimics and down-regulate thymidylate synthase.                                   
     4  docked against a conformational ensemble of thymidylate synthase.                                   
     5 not interfere with intermediate formation at thymidylate synthase.                                   
     6 with the enzymes dihydrofolate reductase and thymidylate synthase.                                   
     7 sential KSHV genes, the viral polymerase and thymidylate synthase.                                   
     8 e next enzyme in the dTTP synthetic pathway, thymidylate synthase.                                   
     9   Compound 3 was also a weak inhibitor of rh thymidylate synthase.                                   
    10 rch Institute against Toxoplasma gondii DHFR-thymidylate synthase.                                   
    11 phate, a tight binding covalent inhibitor of thymidylate synthase.                                   
    12 ate deoxyuridine and coupled the reaction to thymidylate synthase.                                   
    13 ion of antiproliferative agents that inhibit thymidylate synthase.                                   
    14 than one site of action; the primary site is thymidylate synthase.                                   
    15   The approach is illustrated by an example: Thymidylate synthase, a highly conserved enzyme essentia
    16 dium falciparum, dihydrofolate reductase and thymidylate synthase activities are conferred by a singl
  
    18  study we demonstrated that Escherichia coli thymidylate synthase activity could be restored complete
    19 gs is the suggestion that the restoration of thymidylate synthase activity is due to a separation of 
  
  
  
    23 . coli NDP kinase interacts directly with T4 thymidylate synthase, aerobic ribonucleotide reductase, 
    24 of both endogenous and ectopically expressed thymidylate synthase alleles revealed that the mRNA-bind
    25 s applied to generate a potent inhibitor for thymidylate synthase, an essential enzyme in pyrimidine 
    26 and is a major supplier of the substrate for thymidylate synthase, an important enzyme in DNA synthes
    27 negatively charged dihydrofolate produced at thymidylate synthase and a series of lysine and arginine
    28 nse-expressing dones exhibited a decrease in thymidylate synthase and an increase in thymidine phosph
  
    30  enzymes in its biosynthetic pathway, namely thymidylate synthase and cytoplasmic thymidine kinase.  
    31 by the fact that a 100-fold up-regulation of thymidylate synthase and dihydrofolate reductase (known 
    32 and trimethoprim (TOP), potent inhibitors of thymidylate synthase and dihydrofolate reductase, respec
  
    34  thought to kill cells via the inhibition of thymidylate synthase and increased use of dUTP in place 
  
    36 f the basis of half-the-sites reactivity for thymidylate synthase and providing an example of such a 
    37 apeutics, including dihydrofolate reductase, thymidylate synthase and ribonucleotide reductase, while
  
    39 and cellular morphology between H630 and the thymidylate synthase and rTSbeta-overproducing, 5-FU-res
    40 y established determinants of 5-FU response: thymidylate synthase and thymidine phosphorylase activit
    41 ovo thymidylate biosynthesis pathway, cSHMT, thymidylate synthase, and dihydrofolate reductase, all c
  
    43 e equivalent inhibition of the target enzyme thymidylate synthase, and instead accumulate progressive
    44 sical thymidylate synthases, including human thymidylate synthase, and is instrumental in mechanism-b
  
    46 sporter 1 (hENT1), thymidine kinase 1 (TK1), thymidylate synthase, and thymidine phosphorylase (TP) w
    47 n complexes with their in vivo target, human thymidylate synthase, and with the structurally best-cha
    48 tide reductase, dihydrofolate reductase, and thymidylate synthase are coordinately regulated to ensur
  
  
    51 use the enzyme activities of dThd kinase and thymidylate synthase, as well as the levels of triphosph
  
    53 e, Bacillus subtilis expresses two different thymidylate synthases: bsTS-A and bsTS-B. bsTS-A display
  
  
  
  
    58 rom TM0423 glycerol dehydrogenase and TM0449 thymidylate synthase-complementing protein are presented
    59     One mutant, K282E/R283E, was found to be thymidylate synthase-dead because of an impaired ability
    60 es examined, as did thymidine deprivation in thymidylate synthase-deficient (thymidylate synthase-) c
    61 luorouracil in colon cancer, is regulated in thymidylate synthase-deficient (TS(-)) human colon carci
  
    63 luated both in vivo, by complementation of a thymidylate synthase-deficient Escherichia coli mutant, 
    64 uman enzyme with the ability to complement a thymidylate synthase-deficient Escherichia coli strain a
    65 crystal structure of dihydrofolate reductase-thymidylate synthase (DHFR-TS) from Cryptosporidium homi
  
    67 ckout (DKO) lines of dihydrofolate reductase-thymidylate synthase (DHFR-TS) of bloodstream Trypanosom
    68  bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS), the experimentally obser
  
    70 ate cycle (encoding dihy-drofolate reductase-thymidylate synthase, dhfr-ts, and serine hydroxymethylt
    71 pend on the presence of intact gp32, notably thymidylate synthase, dihydrofolate (DHF) reductase, rib
    72 tic methods to characterize the bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) e
    73 ate reductase activity from the bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) i
  
    75 hat substrate channeling in the bifunctional thymidylate synthase-dihydrofolate reductase enzyme from
  
    77 ions of rTS signaling mimics as enhancers to thymidylate synthase-directed chemotherapy, evidence tha
    78 an have great influence over the efficacy of thymidylate synthase-directed chemotherapy, thereby enha
    79 tification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced
    80 2-associated protein), nucleotide synthases (thymidylate synthase), early intermediate genes (early g
  
    82 strate is the pyrimidine biosynthetic enzyme thymidylate synthase (EC 2.1.1.45), which catalyzes the 
  
  
  
  
    87 man pathogens, thyX-encoded flavin-dependent thymidylate synthase (FDTS) catalyzes the last step in t
    88 hyX gene, which codes for a flavin-dependent thymidylate synthase (FDTS), and is present in several h
    89 gens rely on an alternative flavin-dependent thymidylate synthase (FDTS), which differs from the huma
  
  
    92 ium tuberculosis and dihydrofolate reductase/thymidylate synthase from Babesia bovis, against 48 diff
  
    94 crystal structure of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis and a 
  
  
  
    98 ation of a targeted region of the P. carinii thymidylate synthase gene by PCR over the 8-week study p
    99  present study, we identified an orthologous thymidylate synthase gene in the relapsing fever (RF) ag
   100 L. major promastigotes or with dihydrofolate-thymidylate synthase gene locus (DHFR-TS) gene knockout 
   101  homing endonuclease I-TevI that targets the thymidylate synthase gene of phage T4, we readily isolat
   102 orphism in the 3'-untranslated region of the thymidylate synthase gene was shown to influence mRNA st
   103 ich targets a different cleavage site in the thymidylate synthase gene, recapitulating the evolution 
   104  of a plant DHFR-TS (dihydrofolate reductase-thymidylate synthase) gene family that implements the pe
   105  interleukin-6, dihydrofolate reductase, and thymidylate synthase genes were identified, along with a
   106  Expression of a series of six markers (p53, thymidylate synthase, glutathione s-transferase pi [GST-
   107 therapeutic drug pemetrexed, an inhibitor of thymidylate synthase, has an important secondary target 
  
   109 ntiangiogenic effects and also inhibit human thymidylate synthase (hTS) for cytotoxic effects in sing
  
  
  
  
  
   115 ta suggest that BGC 945 selectively inhibits thymidylate synthase in alpha-FR-overexpressing tumors a
  
   117 tive mechanism was proposed based on that of thymidylate synthase, in which the thiol(ate) group of a
   118 ionality has been demonstrated for classical thymidylate synthases, including human thymidylate synth
   119 titute for the IDR and the hA helix of human thymidylate synthase, indicating that the degradation-pr
   120 nd FdU misincorporation sites resulting from thymidylate synthase inhibition and thymine depletion.  
  
   122 r, naphthoquinone 3b has an IC(50) value for thymidylate synthase inhibition that is comparable to FU
  
   124 ng gemcitabine uptake or gemcitabine-induced thymidylate synthase inhibition, and only reflected grow
  
   126 NG depletion does not sensitize cells to the thymidylate synthase inhibitor (raltitrexed), which indu
  
   128 ed by single exposures to a low level of the thymidylate synthase inhibitor 5-fluorouracil (5-FU) or 
  
  
   131  FdUMP[10] as well as to FdUMP, FdU, and the thymidylate synthase inhibitor raltitrexed (Tomudex).   
   132 BGC 945 is a cyclopenta[g]quinazoline-based, thymidylate synthase inhibitor specifically transported 
   133 nses (i.e. G(2) arrest and lethality) to the thymidylate synthase inhibitor, Tomudex, and a greater l
   134 rouracil combined with leucovorin and to the thymidylate synthase inhibitor, ZD9331, dependent on thy
   135 key determinant of tumor cell sensitivity to thymidylate synthase inhibitors such as 5-fluoro-2'-deox
  
   137 positively regulates the cytotoxic action of thymidylate synthase inhibitors, negatively regulates th
  
   139 '-deoxyuridine 5'-monophosphate (FdUMP), the thymidylate synthase inhibitory metabolite of 5-fluorour
  
   141 identity between MJ0757 and Escherichia coli thymidylate synthase is 7%, well below the threshold of 
  
  
   144 e labeled cofactor in mechanistic studies of thymidylate synthase is demonstrated by measuring the tr
   145 owed that intracellular proteolysis of human thymidylate synthase is directed by a degron at the poly
   146 nophages, but also by all 27 T4-like phages (thymidylate synthase); its evolutionary history suggests
   147 tease, dihydrofolate reductase, HIV Tar RNA, thymidylate synthase, kinesin, insulin receptor, tyrosin
  
   149 site CC genotype (OR, 4.5; P =.045), and the thymidylate synthase low activity 2/2 enhancer repeat ge
   150 amples for the detection of polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductas
  
  
   153 lethal to E. coli harboring either wild-type thymidylate synthase or constructs encoding previously c
   154 rent chemical cascade than that of classical thymidylate synthases or any other known biological meth
   155 sites located immediately upstream of ORF70 (thymidylate synthase), ORF19 (tegument protein), and ORF
   156 lasmodium falciparum dihydrofolate reductase-thymidylate synthase (P. falciparum DHFR-TS) with the ob
   157 HFR mRNA, while unrelated proteins including thymidylate synthase, p53 and glutathione-S-transferase 
  
   159 tide reductase, dihydrofolate reductase, and thymidylate synthase promoters in the absence of SWI/SNF
  
   161 actone (3-oxo-C12-(L)-HSL) can down-regulate thymidylate synthase protein at 10 micromol/L and reduce
   162 was specific, because thymidylate kinase and thymidylate synthase protein levels were not decreased n
  
  
   165 exocyclic methylene-dUMP intermediate in the thymidylate synthase reaction was recently obtained by d
   166 ase is required to significantly inhibit the thymidylate synthase reaction, consistent with experimen
  
   168 ar hormone receptors with a highly sensitive thymidylate synthase reporter, yield simple sensors that
   169 ourses (R(2) = 0.043; P < .001), whereas the thymidylate synthase rs34743033 tandem repeat polymorphi
  
   171 ybaK for its ability to suppress the E. coli thymidylate synthase thyA:146CCA missense mutant strain,
   172  were derived from three different antigens: thymidylate synthase (ThyA(30-38)), RNA polymerase beta-
   173 cobacterium bovis BCG with insertions in the thymidylate synthase (thyA) gene, a critical determinant
  
   175 eles enhanced the survival of L. pneumophila thymidylate synthase (thyA)-deficient strains, which can
  
   177 nucleotide salvage, such as flavin-dependent thymidylate synthase, thymidylate kinase, ribonucleotide
  
  
  
   181 se thymine depends on activity of the enzyme thymidylate synthase to catalyse the methylation of the 
   182 zation of dihydrofolate reductase, SHMT, and thymidylate synthase to the nuclear lamina, indicating t
   183 se (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS enhancer region and 3' untransl
   184 uced folate carrier (RFC) 80A allele and the thymidylate synthase (TS) 3'-untranslated region (3'-UTR
   185  the presence of adequate dTTP pools, normal thymidylate synthase (TS) activity, persistence of incre
   186 ymidine to overcome the potent inhibition of thymidylate synthase (TS) and deoxycytidine monophosphat
   187 onclassical analogues 5-17 as potential dual thymidylate synthase (TS) and dihydrofolate reductase (D
  
   189 and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (D
   190 rotozoal parasites are unusual in that their thymidylate synthase (TS) and dihydrofolate reductase (D
   191 nd synthesized as a potent dual inhibitor of thymidylate synthase (TS) and dihydrofolate reductase (D
   192 ues 2a-2m were synthesized as potential dual thymidylate synthase (TS) and dihydrofolate reductase (D
   193 gues 5-13 were synthesized as potential dual thymidylate synthase (TS) and dihydrofolate reductase (D
   194 nclassical analogues 5- 15 as potential dual thymidylate synthase (TS) and dihydrofolate reductase (D
   195 lls resulted in corresponding high levels of thymidylate synthase (TS) and resistance to 5-fluoropyri
  
  
   198 llus casei, Escherichia coli, and rat and rh thymidylate synthase (TS) and were found to be weak inhi
  
  
  
  
  
  
   205 rements for I-TevI, which binds a stretch of thymidylate synthase (TS) DNA that codes for functionall
  
   207 s have investigated the relationship between thymidylate synthase (TS) expression and survival in col
   208 e thyX gene and depend upon the conventional thymidylate synthase (TS) for their dTMP requirements.  
  
   210 oded by a group I intron that interrupts the thymidylate synthase (TS) gene (thyA) of Bacillus mojave
  
  
   213 folate compounds, developed as inhibitors of thymidylate synthase (TS) in a strategy to circumvent dr
   214      The role of Ser 167 of Escherichia coli thymidylate synthase (TS) in catalysis has been characte
   215 nd possibly more effective way of inhibiting thymidylate synthase (TS) in cells than through the use 
   216 s to investigate the utility of quantitating thymidylate synthase (TS) in the primary tumor as a surr
   217 PYD expression by p53 is augmented following thymidylate synthase (TS) inhibition and DPYD repression
  
   219  now known as ONX 0801), is a small molecule thymidylate synthase (TS) inhibitor discovered at the In
   220 sing levels of dUTPase on sensitivity to the thymidylate synthase (TS) inhibitor fluorodeoxyuridine (
   221 and toxicity of clinically used folate-based thymidylate synthase (TS) inhibitors that require folylp
  
  
  
  
   226 to fluoropyrimidines and other inhibitors of thymidylate synthase (TS) is a serious problem often ass
  
  
  
  
  
  
  
   234 ur laboratory have shown that translation of thymidylate synthase (TS) mRNA is controlled by its own 
  
  
  
  
   239 ies have shown that the repressive effect of thymidylate synthase (TS) mRNA translation is mediated b
   240  antimetabolite radiosensitizers may inhibit thymidylate synthase (TS) or ribonucleotide reductase, a
   241 R) and antifolate-resistant mutants of human thymidylate synthase (TS) that contain single residue su
   242  encoding dihydrofolate reductase (DHFR) and thymidylate synthase (TS) was cloned from a Zea mays cDN
   243 esidues on the RNA binding activity of human thymidylate synthase (TS) was investigated by mutating e
   244 8-bp tandem repeat in the promoter region of thymidylate synthase (TS) were studied and found to modu
  
  
  
  
   249 tifolates on dihydrofolate reductase (DHFR), thymidylate synthase (TS), and folylpolyglutamate synthe
  
   251 e LY231514 were synthesized as inhibitors of thymidylate synthase (TS), dihydrofolate reductase (DHFR
  
  
   254 irreversible inactivator of Escherichia coli thymidylate synthase (TS), which covalently modifies Tyr
   255 onucleases that bind a homologous stretch of thymidylate synthase (TS)-encoding DNA but use different
  
   257 degraded siRNAs reversed the cytotoxicity of thymidylate synthase (TS)-targeted siRNAs and other TS i
  
  
  
  
  
  
  
  
   266 athway is the pyrimidine biosynthetic enzyme thymidylate synthase (TS; EC 2.1.1.45), which catalyzes 
   267     Based on crystal structures of bacterial thymidylate synthases (TS), a glutamine corresponding to
  
  
  
  
   272 es are involved in the reaction catalyzed by thymidylate synthase (TSase), which provides the sole de
  
  
  
   276 enetetrahydrofolate reductase (MTHFR) 677TT, thymidylate synthase (TSER) *2/*2 (variable number of ta
  
   278 s examined and haplotypes generated included thymidylate synthase (TYMS 28-bp triple repeat [3R]-->do
   279 , where they form a multienzyme complex with thymidylate synthase (TYMS) and dihydrofolate reductase 
   280 hylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) are known to play a role in 
   281 uiescence through the cell cycle, regulating thymidylate synthase (Tyms) expression at the G(1)/S bou
   282 ng required for activating expression of the thymidylate synthase (Tyms) gene at the G1/S transition.
   283 erest because it contained the gene encoding thymidylate synthase (TYMS), a molecular target of 5-FU.
   284 ial serine hydroxymethyltransferase (SHMT2), thymidylate synthase (TYMS), and a novel human mitochond
   285 ymes serine hydroxymethyltransferase (SHMT), thymidylate synthase (TYMS), and dihydrofolate reductase
   286 he transcriptional status of four key genes, thymidylate synthase (TYMS), MORF-related gene X (MRGX),
  
   288 seem, based on accumulated literature, to be thymidylate synthase (TYMS, TS) expression levels, TS ge
  
   290 yed in their appearance included viral DHFR, thymidylate synthase, vMIP I, G protein-coupled receptor
   291 me's specific activity, it was proposed that thymidylate synthase was a half-of-the-sites activity en
  
   293   Using mutants of the C-terminal residue of thymidylate synthase, we found that the ratio of HETM-dU
   294 s, rely on the thyA- or TYMS-encoded classic thymidylate synthase, whereas, certain microorganisms, i
   295 olypeptide (DHFR-TS, dihydrofolate reductase-thymidylate synthase) which assembles into a functional 
  
   297 ide thymidylate is synthesized by the enzyme thymidylate synthase, which catalyzes the reductive meth
   298 trexed that combines enzymatic inhibition of thymidylate synthase with alpha-folate receptor-mediated
  
  
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