Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “THIAZOLES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed1993

Heterodimeric DNA-binding dyes designed for energy transfer: stability and applications of the DNA complexes.

Spectroscopic studies of the complexes of double-stranded (ds) DNA with the polymethylene-amine linked heterodimers thiazole orange-thiazole blue, thiazole orange-ethidium, and fluorescein-ethidium, in each case show efficient energy transfer from donor to acceptor chromophores (Benson, S.C., Singh, P. and Glazer, A.N. (1993) accompanying manuscript). A quantitative assay of the stability of such complexes during gel electrophoresis is presented. The off-rate of dye from complexes formed at an initial dsDNA bp:dye ratio > or = 10:1 follows strict first-order kinetics. The t0.5 values for the dissociation of a series of related dyes provide a quantitative criterion for the design of DNA-binding fluorophores. Complexes of dsDNA with the monomeric propidium and cyanine dyes, [1-(9-amino-4,7-diazanonyl)-3,8-diamino-6-phenyl-phenanthridinium bromide trihydrobromide] and (N,N'-tetramethyl-1,3-propanediamino)propyl thiazole orange [4-[3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidenyl]-1-(4 ,4,8-trimethyl-4,8-diazanonyl)-quinolinium diiodide], are much more stable than those with their widely used counterparts, ethidium and thiazole orange. Applications of the new dyes in post-staining of gels and in the multiplex detection of DNA restriction fragments are presented.

DNA↗
PubMed1982

Mass spectrometry of 2-substituted-4-arylthiazoles. II--Identification of microsomal nitroreduction product by mass spectrometry.

Electron impact fragmentation of 2-methyl-4-(4-nitrophenyl)-thiazole and 2-amino-4-(4-nitrophenyl)-thiazoles were studied. Prominent fragment ions result from: (1) elimination of an NO2 radical and of a neutral NO molecule; (2) 1,2 cleavage of the thiazole ring in both compounds to give a phenoxythiirene ion; and (3) subsequent cleavage of this phenoxythiirene ion to give the common ions [C7H5]+ and [C5H3]+. An anaerobic microsomal nitroreduction product of 2-methyl-4-(4-nitrophenyl) thiazole was isolated and its structure was determined by electron impact, chemical ionization and high resolution mass spectrometry to be 2-methyl-4-(4-aminophenyl)-thiazole.

Animals↗
PubMed1966

Observations on the biosynthesis of thiamine in yeast.

1. Methods are described for the isolation of radioactively pure thiamine from yeast and its degradation on a small scale to its cyclic components. 2. A degradation of the pyrimidine ring and a thin-layer method for the separation of thiamine, its derivatives and pyrimidine and thiazole residues are described. 3. [(14)C]Formate is more effectively incorporated into the pyrimidine residue than into the thiazole residue, whereas the reverse is true with l-[Me-(14)C]methionine. 4. Experiments with [Me-(14)C,(35)S]methionine demonstrate that methionine provides an intact unit for the biosynthesis of the thiazole ring. 5. [6-(14)C]Orotic acid is insignificantly incorporated into the pyrimidine residue of thiamine. 6. Experiments with [1-(14)C]- and [2-(14)C]-acetate indicate that it is incorporated as a unit into the thiazole residue, but that only C-2 is incorporated into the pyrimidine residue. 7. l-[U-(14)C]Alanine is also effectively incorporated into the thiazole residue. 8. These results are discussed in relation to possible pathways of biosynthesis of the two ring components of the thiamine molecule.

Acetates↗
PubMed1968

Biosynthesis of thiamine. Incorporation experiments with 14C-labelled substrates and with (15N)glycine in Saccharomyces cerevisiae.

1. Yeast was grown in a minimal synthetic medium together with a range of (14)C-labelled substrates under standardized conditions. After isolation, the purified thiamine was cleaved by sulphite and the pyrimidine and thiazole moieties were purified and assayed for radioactivity. 2. In order of decreasing incorporation, [(14)C]formate, [3-(14)C]serine, [2-(14)C]glycine and [2-(14)C]acetate supplied label for the pyrimidine, and [2-(14)C]glycine, [3-(14)C]serine, [1-(14)C]glycine, [(14)C]formate and [2-(14)C]acetate for the thiazole. Incorporation of label into the fragments from several other (14)C-labelled substrates, including [Me-(14)C]- and [3,4-(14)C(2)]-methionine, was insignificant. 3. [3-(14)C]Serine was shown not to contribute label to C-2 of the thiazole ring. 4. Significant incorporation of nitrogen from [(15)N]glycine into the thiazole moiety, but not into the pyrimidine moiety, was established. 5. It appears that C-2 and N-3 of the thiazole ring are formed from C-2 and the nitrogen atom of glycine, but the entire methionine molecule does not appear to be implicated.

Acetates↗
PubMed1982

Isolation of single-site Escherichia coli mutants deficient in thiamine and 4-thiouridine syntheses: identification of a nuvC mutant.

A method is described to rapidly select and classify many independent near-UV irradiation-resistant Escherichia coli mutants, which include tRNA modification and RNA synthesis control mutants. One class of these mutants was found to be simultaneously deficient in thiamine biosynthesis and in the ability to modify uridine in tRNA to 4-thiouridine, known to be the target for near-UV irradiation. These mutants were found to be unable to make thiazole, a thiamine precursor. The addition of thiazole restores the thiamine deficiency but does not render the cells near-UV irradiation sensitive. In vitro studies on one of these mutants indicated a deficiency in protein factor C (nuvC), required for the 4-thiouridine modification of tRNA. In P1 transduction, the thiazole marker cotransduced with the histidine marker, which places the thiazole marker between 42 and 46 min on the E. coli chromosome map. Both thiamine production and 4-thiouridine production were resumed by 87% of the spontaneous reversions, suggesting a single-point mutation. Our results indicate that we have isolated nuvC mutants and that the nuvC polypeptide is involved in two functions, tRNA modification and thiazole biosynthesis.

Chromosome Mapping↗
PubMed1994

C-glycosyl bond conformation in oxazofurin: crystallographic and computational studies of the oxazole analogue of tiazofurin.

Oxazofurin is the inactive oxazole analogue of the C-glycosyl thiazole antitumor agent tiazofurin. Replacement of the thiazole sulfur in tiazofurin with the oxazole oxygen in oxazofurin produces conformational effects that are examined using crystallographic and computational methods. The crystal structure of oxazofurin contains six molecules in the asymmetric unit and has been refined to a standard R value of 6.8% for all data. The six oxazofurin conformers show an average C-glycosidic torsion angle of 70(9) degrees. This value is significantly higher than the average absolute C-glycosidic torsion angle of 24(10) degrees obtained from previous thiazole nucleoside structures. Previous studies suggest that, in tiazofurin, an electrostatic interaction between a positively charged thiazole sulfur and negatively charged furanose oxygen constrains the C-glycosidic torsion angle to a relatively small value. Ab initio molecular orbital studies presented here suggest that the higher C-glycosidic angles observed in the oxazofurin structures result from a repulsive interaction between negatively charged oxazole and furanose oxygens. Thus, it is likely that differences in activity between oxazo- and tiazofurin are either (1) due directly to differences in electronic properties between the thiazole and oxazole rings or (2) due to the variation in C-glycosidic bond conformation resulting from the alteration in the charge distribution of the heterocycle.

Antineoplastic Agents↗
PubMed1984

Mass spectrometry of 2-substituted-4-arylthiazoles. 3--Identification of microsomal nitroreduction products by mass spectrometry.

The electron impact mass spectra of the chemical carcinogens 4-(4-nitrophenyl)-2- methylaminothiazole , 4-(4-aminophenyl)-2- methylaminothiazole and 4-(4-aminophenyl)-2- aminothiazole were studied. The 4-(4-amino-phenyl)-2-substituted thiazoles were isolated from the anaerobic microsomal reduction of their respective 4-nitrophenyl analogues. Microsomes prepared from rat and rabbit kidney tissues were used. The identity of the reduction products were established by chemical synthesis and mass spectrometry. The mass spectrometric fragmentation of the nitro derivative shows prominent ions arising from the loss of the nitro group, ring enlargement of the thiazoles, and the phenylthiirene ion resulting from 1,2-cleavage of the thiazole ring. In the 4-(4-aminophenyl)-2-substituted amino derivative prominent ions result from the preferential 1,2-cleavage of the thiazole ring to give the common 2-(4-aminophenyl) thiirene ion and subsequent fragmentation of this ion.

Aniline Compounds↗
PubMed1992

Reticulocyte quantification by flow cytometry, image analysis, and manual counting.

Reticulocyte counting by flow cytometry with thiazole orange was compared to manual or automated counting of new methylene blue stained blood smears. Forty-nine samples were compared for manual counting from randomly chosen clinical samples. Two hundred and eighty-nine samples from bone marrow transplant patients were compared during the period before and through chemo-irradiation and engraftment. The slopes of correlation plots were less than 1 when flow cytometric data were the dependent variable, suggesting that thiazole orange is less sensitive than new methylene blue. In a third study, 407 samples from bone marrow transplant patients were compared after increasing the thiazole orange concentration. The reticulocyte fluorescence distribution was divided into four groups of the brightest (youngest) 40, 60, 80, and 100% of reticulocytes. The slopes from regression analysis were 0.25, 0.49, 0.78, and 1.14, respectively. This demonstrates that thiazole orange is more sensitive than new methylene blue because the window of analysis includes an increased fraction of mature reticulocytes. In addition, the precision of each assay as measured. The rank order of precision from high to low was flow cytometry > image analysis >> manual counting.

Benzothiazoles↗
PubMed1995

Fluorescence energy-transfer cyanine heterodimers with high affinity for double-stranded DNA. I. Synthesis and spectroscopic properties.

We have designed, synthesized, and characterized fluorescent cyanine heterodimers that exploit resonance energy transfer to achieve strong emission above 650 nm with 488-nm excitation. Thiazole orange serves as the common fluorescence donor in these dyes and thiazole-indolenine, thiazole blue, or symmetric thiazole blue as acceptors. The donor and acceptor chromophores are linked by a polymethylene linker containing quaternary amino groups. These heterodimers have a high affinity for double-stranded DNA (dsDNA). The donor emission in the dsDNA-bound dyes is quenched by over 85%. The affinity for dsDNA and the quenching of donor fluorescence were optimized by varying the length of the linker between the donor and acceptor. Complexes of dsDNA fragments with such optimized dyes dissociated very slowly (t(0.5) > 300 min) during agarose gel electrophoresis.

DNA↗
PubMed1995

Fluorescence energy-transfer cyanine heterodimers with high affinity for double-stranded DNA. II. Applications to multiplex restriction fragment sizing.

Energy-transfer cyanine dyes, a thiazsole orange-thiazole-indolenine (butylTOTIN) and a thiazole orange-thiazole blue heterodimer (pentylTOTAB), form high-affinity complexes with double-stranded (ds)DNA with donor fluorescence (lambdaF(max)527 nm) quenched >90% and with acceptor fluorescence emission above 650 nm (S. C. Benson, Z. Zeng, and A. N. Glaser (1995) Anal. Biochem. 231, 247-255). After separation by agarose gel electrophoresis, bands of precomplexed dsDNA-dye restriction fragments containing 10 pg of dsDNA are readily detected with a laser-excited confocal-fluorescence gel scanner (R. A. Mathies et al. (1994) Rev. Sci. Instrum. 65, 807-812) following donor excitation at 488 nm (argon ion laser) or direct acceptor excitation at 647 nm (krypton ion laser). Accurate two-color multiplex sizing of restriction fragments is obtained with 488-nm excitation with dsDNA fragments precomplexed with thiazole orange dimer (TOTO) as unknowns (detected at 500-565 nm, green channel) and dsDNA fragments stained with the energy-transfer cyanine dyes (detected at 645-750 nm, red channel) as internal standards. There is negligible cross talk of fluorescence between the red and green channels and no significant dye migration in mixtures of prelabeled standard and unknown fragments.

DNA↗
PubMed1993

The induction of cytochrome P4502E1 by nitrogen- and sulfur-containing heterocycles: expression and molecular regulation.

Several structurally related sulfur- and nitrogen-containing heterocycles including thiazole, pyrazine, pyridazine, pyrimidine, thiophene, and triazole, which are present in tobacco, tobacco smoke, and certain foods, have been employed with the goal of characterizing the effects of these agents on the inhibition and expression of P4502E1 in hepatic tissue and on the molecular level regulatory events governing enhanced expression. The results of this study reveal that whereas the binding constants of these compounds to 2E1 moderately correlated with the percentage inhibition of metabolic activity in vitro (r = 0.66), neither inhibition of metabolic activity nor binding to P4502E1 correlated with relative induction of P4502E1 levels (r = 0.07 and 0.03, respectively). Thiazole, which produced the greatest inhibition of metabolic activity (88%) and exhibited the highest binding affinity for P4502E1 (35 microM), induced P4502E1 approximately fourfold. In contrast, pyrazine and pyridazine, which only marginally inhibited metabolic activity (54 and 41%, respectively), and weakly bound 2E1 (73 and 384 microM, respectively), increased P4502E1 levels approximately four- and fivefold, respectively. A common feature associated with these inducers, however, was the substantial decrease in hepatic P4502E1 poly(A)+ RNA levels in treated animals relative to untreated animals. Slot and Northern blot hybridization analyses revealed an approximately 80% decrease in P4502E1 poly(A)+ RNA levels at 48 hr following treatment of rats with thiazole, and at 24 hr following treatment of animals with either pyrazine or pyridazine, relative to controls. P4502E1 poly(A)+ RNA levels appeared to increase gradually, returning to levels which approximated 60% of the P4502E1 poly(A)+ RNA levels present in untreated animals at 48 and 72 hr following treatment with pyrazine or pyridazine, respectively. The results of these experiments show that thiazole, pyrazine, and pyridazine induce P4502E1 in rats, that the induction of 2E1 is associated with a concomitant decrease in 2E1 poly(A)+ RNA levels, and that these agents differentially affect the expression of P4502E1.

Animals↗
PubMed1998

Kinetics and regioselectivity of peptide-to-heterocycle conversions by microcin B17 synthetase.

BACKGROUND: The Escherichia coli peptide antibiotic microcin B17 (MccB17) contains four oxazole and four thiazole rings introduced post-translationally in the 69 amino acid McbA gene product, an MccB17 precursor, by the microcin B,C,D enzyme complex. Both monocyclic and 4,2-bis-heterocyclic moieties are generated. The enzymatic cyclization involves 14 of the last 43 amino acids of McbA and requires the presence of the first 26 amino acids that function as a specificity-conferring propeptide. RESULTS: We have constructed maltose-binding protein (MBP)-McbA1-46 fusion proteins and have mutagenized the Gly39-Ser40-Cys41 (GSC) wild-type sequence to assess the regioselectivity and chemoselectivity of MccB17-synthetase-mediated heterocycle formation at the first two loci, residues 40 and 41 of McbA. Four single-site and four double-site substrates showed substantial differences in turnover as assessed by western assays, UV-visible spectroscopy and mass spectrometry. Cysteine-derived thiazoles form at a greater rate than serine-derived oxazoles. Formation of bis-heterocycles is sensitive both to composition and sequence context. CONCLUSIONS: The E. coli McbB,C,D MccB17 synthetase is the first peptide heterocyclization enzyme to be characterized. This study reveals substantial regioselectivity and chemoselectivity (thiazole > oxazole) at the most amino-terminal bis-heterocyclization site of McbA. The heterocyclization of GSS and GCC mutants of McbA1-46 by MccB17 synthetase demonstrates that the complex can efficiently generate tandem bis-oxazoles and bis-thiazoles, moieties not found in MccB17 but present in natural products such as hennoxazole and bleomycin. The observations suggest a common enzymatic mechanism for the formation of peptide-derived heterocyclic natural products.

Anti-Bacterial Agents↗
PubMed2000

Fluorescent and photochemical properties of a single zinc finger conjugated to a fluorescent DNA-binding probe.

A single zinc finger derived from the DNA-binding domain of the glucocorticoid receptor (GR) has been tethered to the intercalating fluorophore thiazole orange, and the DNA recognition characteristics of the conjugate have been examined. DNA sequence specificity for the peptide-dye conjugate, determined by steady-state fluorescence measurements and photoactivated DNA cleavage experiments, reproduce the binding features of response element recognition found in the native GR. The thiazole orange is able to intercalate and fluoresce when the conjugate binds, at concentrations where little fluorescence is observed from either the conjugate alone or the conjugate mixed with DNA lacking the zinc finger target sequence. The conjugate preferentially targets a 5'-TGTTCT-3' sequence (the native glucocorticoid receptor element) with a dissociation constant of about 25 nM. Lower binding affinities (up to 10-fold) are observed for single site variants of this sequence, and much lower affinity (40-50-fold) is observed for binding to the estrogen response element (which differs from the glucocorticoid receptor element at two positions) as well as to nonspecific DNA. Footprinting reactions show a 4-6 base pair region that is protected by the zinc finger moiety. Photocleavage assays reveal a several base pair region flanking the recognition sequence where the tethered thiazole orange moiety is able to intercalate and subsequently cleave DNA upon visible light exposure. Thiazole orange is also shown to oxidize the 5'-G of remote GG sequences, depending on the details of the intervening DNA sequence. Small synthetic protein-dye conjugates such as this one are potentially useful for a variety of purposes including sequence-specific probes that work under physiological conditions (without melting and hybridization of DNA), sequence-specific photocleavage agents, and self-assembling components in electron and energy transfer systems that utilize DNA as a scaffold and/or photochemical medium.

Base Sequence↗
PubMed2005

Total synthesis of the thiopeptide antibiotic amythiamicin D.

The thiopeptide (or thiostrepton) antibiotics are a class of sulfur containing highly modified cyclic peptides with interesting biological properties, including reported activity against MRSA and malaria. Described herein is the total synthesis of the thiopeptide natural product amythiamicin D, which utilizes a biosynthesis-inspired hetero-Diels-Alder route to the pyridine core of the antibiotic as a key step. Preliminary studies using a range of serine-derived 1-ethoxy-2-azadienes established that hetero-Diels-Alder reaction with N-acetylenamines proceeded efficiently under microwave irradiation to give 2,3,6-trisubstituted pyridines. The thiazole building blocks of the antibiotic were obtained by either classical Hantzsch reactions or by dirhodium(II)-catalyzed chemoselective carbene N-H insertion followed by thionation, and were combined to give the bis-thiazole that forms the left-hand fragment of the antibiotic. The key Diels-Alder reaction of a tris-thiazolyl azadiene with benzyl 2-(1-acetylaminoethenyl)thiazole-4-carboxylate gave the core tetrathiazolyl pyridine, which was elaborated into the natural product by successive incorporation of glycine and bis-thiazole fragments followed by macrocyclization.

Anti-Bacterial Agents↗
PubMed1966

The control mechanism of thiamine biosynthesis a model for the study of control of converging pathways.

1. Thiamine or the pyrimidine moiety of thiamine added in excess to a growing culture of Salmonella typhimurium LT2 repressed subsequent thiamine synthesis in non-growing organisms. 2. A mutant unable to convert added pyrimidine moiety into thiamine was not repressible by the pyrimidine, showing that thiamine, not the pyrimidine, was the repressor. 3. Thiamine repression occurred at 40mmug. of thiamine/mg. dry wt. or above and de-repression occurred at 30mmug. of thiamine/mg. dry wt. or below. 4. Thiamine controlled the pyrimidine and thiazole pathways at the same concentration and to the same extent. 5. Biosynthesis of the thiazole moiety had, in contrast with biosynthesis of the pyrimidine moiety, an additional feedback inhibition control that allowed utilization of the exogenous thiazole. 6. The enzymes joining the pyrimidine and thiazole moieties were repressible by high concentrations of thiamine. 7. Thiamine was rapidly converted into thiamine pyrophosphate and this appeared to be the active repressor. 8. Theoretical aspects of control of converging pathways are discussed.

Biological Assay↗
PubMed2001

Inhibition of human DNA topoisomerase I by new DNA minor groove ligands: derivatives of oligo-1,3-thiazolecarboxamides.

A series of novel thiazole-containing oligopeptides (oligo-1,3-thiazolecarboxamides) interesting specifically with the minor groove of DNA was shown to inhibit human DNA topoisomerase I (topo I). Inhibitory effects of thiazole-containing oligopeptides (TCO) increase with the number of thiazole units in such compounds. Inhibitory properties of TCO containing 3 or 4 thiazole units were shown to be 3-10 times better than those of the well-known natural antibiotic, distamycin A containing pyrrole rings. The structure of various additional groups attached to the N-terminus and C-terminus of TCO had no significant effect on TCO interaction with the complex of DNA and topo I. TCO were shown to be capable of binding with double-stranded DNA (dsDNA), and the majority of TCO analyzed were more effective in binding with dsDNA than distamycin A. Possible reasons for the different effects of distamycin A and TCO on the reaction of relaxation catalyzed by topo I are discussed.

Base Sequence↗
PubMed1992

Structures of the 4-cyano and 4-methylamidate analogs of tiazofurin.

4-Cyanotiazofurin [2-(beta-D-ribofuranosyl)thiazole-4-carbonitrile, (1)], C9H10N2O4S, M(r) = 242.3, monoclinic, P2(1), a = 7.329(1), b = 8.295 (1), c = 8.697(1) A, beta = 90.90 (1) degree, V = 528.7(1) A3, Z = 2, Dx = 1.52 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 27.2 cm-1, F(000) = 252, T = 293 K, R = 0.0487 for all 1171 unique reflections. 4-Methylamidatetiazofurin [methyl 2-(beta-D-ribofuranosyl)thiazole-4-carboximidate, (2)], C10H14N2O5S, M(r) = 274.3, orthorhombic, P2(1)2(1)2(1), a = 8.596(1), b = 11.060(1), c = 26.064(1) A, V = 2478.1(2) A3, Z = 8, Dx = 1.47 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 24.5 cm-1, F(000) = 1152, T = 293 K, R = 0.0374 for all 2902 unique reflections. Compound (2) crystallizes with two crystallographic unique structures in the asymmetric unit [(2a) and (2b)]. All three structures show a close contact between the thiazole sulfur and the pentose oxygen O(1'). S...O(1') distances are 2.936 (3) A in (1), 2.773 (2) A in (2a) and 2.878 (2) A in (2b), resulting from C-glycosidic torsion angles of 34.5 (4), 15.6 (3) and 27.2 (3) degrees respectively. This interesting feature is conserved in the crystal structures of other thiazole nucleosides [Burling & Goldstein (1992).

Antineoplastic Agents↗
PubMed1967

Growth inhibition by hexoses of a temperature-sensitive thiazoleless mutant of Salmonella typhimurium.

A Salmonella typhimurium mutant showing impairment in the utilization of hexoses was isolated after treatment with N-methyl-N'-nitro-N-nitrosoguanidine. At 30 C, it grew with hexoses (glucose, fructose, galactose, mannitol), glycerol, succinate, or acid-hydrolyzed casein. At 37 C, it failed to grow with any of the hexoses. Enzymatic determinations demonstrated, however, that the enzymes of the glycolytic pathway (up to the formation of triose phosphates) were present and active at 25 and 32 C. At 42 C, the mutant did not grow with any of the carbon sources used. At both 37 and 42 C, the mutant grew perfectly well with hexoses if yeast extract was present. The metabolite required for growth was thiamine or, specifically, its thiazole moiety. If glucose was added to a culture growing in glycerol, at 37 C, growth was inhibited. This inhibition was relieved by the addition of thiamine or thiazole. Thus, at 37 C and only in the presence of hexoses, the mutant manifests a requirement for thiazole. This auxotrophy is absolute at 42 C. These data indicate that, in this mutant, some derivative of hexoses inhibits the synthesis of thiazole, and that this inhibition is also dependent on the temperature of incubation. The position in the bacterial chromosome of the genetic locus of this lesion (thz(-)) was determined by conjugation and found to coincide with the only thiamine (thi) locus so far reported.

Chromosome Mapping↗