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Pyrimidines
Terms modified by Pyrimidines Selected AbstractsDynamic Stereochemical Behaviour of Congested Ruthenium(II) Complexes Containing Asymmetric Thioether Ligands Based on Pyridine and PyrimidineEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 30 2008Giuseppe Tresoldi Abstract The asymmetric thioethers L [L = 2-pyridylmethyl 2,-pyrimidyl sulfide (pps) and 2-(4-methylpyrimidyl) 2,-pyridylmethyl sulfide (mps)] reacted with cis -[RuCl2(N,N -L,)2] [L, = di-2-pyridyl sulfide (dps); 2,2,-bis(4-methylpyridyl) sulfide (4mdps); 2,2,-bis(5-methylpyridyl) sulfide (5mdps)] to give the five-membered-ring chelate complexes [Ru(N,N -L,)2(Npyridine,S -L)]++ as the major products (92,95,%). Because the sulfur and ruthenium atoms are stereogenic centres, with (R) and (S) and , and , configurations, respectively, four isomers, including the enantiomers were obtained. At low temperature and in the methylene region of the 1H NMR spectra, two AB systems due to the enantiomer couples ,S ,R (a) and ,R ,S (b) were observed with abundances of 77,89 and 6,18,%, respectively. Furthermore, NMR spectroscopic investigations showed that the hybrid polydentate ligands L change their coordination mode. Thus, although a and b largely predominate, a mixture of species containing L and the Ru(N,N -L,)2 unit in the ratio 1:1 are present. The four-membered-ring chelate complexes [Ru(N,N -L,)2(Npyrimidine,S -L)]++ (c), as minor species (abundance 1,8,%), are always observed, whereas the dinuclear species [{Ru(N,N -L,)2}2(,-L)2]+4 (d, e) are observed when L, = dps or 5mdps. In these cases, four AB systems are assigned to dinuclear species d and e containing two bridging L that act as Npyridine,S- or Npyridine,Npyrimidine -donor ligands. The 1H NMR spectra are temperature dependent in that at low temperature the complexes undergo inversion of the chiral centre of the coordinated sulfur atom (a [rlhar2] b) and the dimer (d, e) and monomer (c) are in equilibrium; at higher temperatures the complexes undergo a structural dynamic rearrangement, which involves exchange between the coordinated and uncoordinated N atoms (b [rlhar2] c). One-dimensional band-shape analysis of the exchanging methylene and methyl proton signals showed that the energy barriers for inversion of the sulfur centre are in the 50,53 kJ,mol,1 range, whereas those for the higher-temperatures process are in the 62,68 kJ,mol,1 range. The possible mechanisms of the processes are discussed. NMR spectroscopic findings suggest that inversion at the sulfur centre occurs without any bond rupture, whereas the exchange, at higher temperatures (b [rlhar2] c), is a dissociative process involving the breaking of a Ru,Npyridine bond.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Molecular characterization of six unrelated Italian patients affected by pyrimidine 5,-nucleotidase deficiencyBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2003Paola Bianchi Summary. Pyrimidine 5,-nucleotidase deficiency is a rare autosomal recessive disorder characterized by haemolytic anaemia, marked basophilic stippling and accumulation of pyrimidine nucleotides within the erythrocytes. The gene encoding for this enzyme (P5,N-1) has been cloned recently, and seven mutations have so far been identified in 11 unrelated families. We describe the haematological and molecular characteristics of six unrelated Italian patients affected by pyrimidine 5,-nucleotidase deficiency (one from northern and five from southern Italy). The sequence of the complete P5,N-1 gene showed the presence of four different new mutations: a missense mutation AAT,AGT at codon 190 (Asn,Ser), one splicing mutation (IVS9-1 g-c) and two frameshift mutations, DelG576 and InsGG743. Although the molecular defect was homozygous in all patients but one, parents' consanguinity could be confirmed in only one case. InsGG743 was detected in two cases, and DelG576 was found in three patients originating from southern Italy, suggesting a possible geographical distribution of the genetic defect. Haematological data showed the presence of peripheral spherocytosis in all cases, although only one had a concomitant membrane defect. An increase in serum ferritin levels was observed in the splenectomized patients, suggesting that the iron status of these subjects should be monitored and that they should be investigated for potential additional risk factors for iron accumulation. [source] ChemInform Abstract: Electro-Organic Synthesis of New Pyrimidine (III) and Uracil Derivatives (V).CHEMINFORM, Issue 24 2010Saied Saeed Hosseiny Davarani Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Zinc Oxide,Tetrabutylammonium Bromide Tandem as a Highly Efficient, Green, and Reusable Catalyst for the Michael Addition of Pyrimidine and Purine Nucleobases to ,,,-Unsaturated Esters under Solvent-Free Conditions.CHEMINFORM, Issue 39 2008Abdolkarim Zare Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Regioselective N-Arylation of Some Pyrimidine and Purine Nucleobases.CHEMINFORM, Issue 17 2007Ali Khalafi-Nezhad Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Catalytic C,C Coupling Reactions at Nickel by C,F Activation of a Pyrimidine in the Presence of a C,Cl Bond: The Crucial Role of Highly Reactive Fluoro Complexes.CHEMINFORM, Issue 48 2005Andreas Steffen Abstract For Abstract see ChemInform Abstract in Full Text. [source] Synthesis of Pyrazoline, Pyrimidine and 1,5-Benzodiazepine Derivatives of 1,8-Naphthyridine and Evaluation of Antibacterial Activity.CHEMINFORM, Issue 24 2003K. Mogilaiah Abstract For Abstract see ChemInform Abstract in Full Text. [source] Pyrimidine as Constituent of Natural Biologically Active CompoundsCHEMISTRY & BIODIVERSITY, Issue 1 2005Irene This review describes the various manifestations of the pyrimidine system (alkylated, glycosylated, benzo-annelated.). These comprise pyrimidine nucleosides as well as alkaloids and antibiotics , some of them have been discovered and isolated from natural sources already long time ago, others have been reported very recently. A short overview on pyrimidine syntheses (prebiotic synthesis, biosynthesis, and metabolism) is given. The biological activities of most of the pyrimidine analogs are briefly described, and, in some cases, syntheses are formulated. [source] Synthesis of Aryl-Substituted Pyrimidines by Site-Selective Suzuki,Miyura Cross-Coupling Reactions of 2,4,5,6-TetrachloropyrimidineADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 9 2010Munawar Hussain Abstract Suzuki,Miyaura reactions of 2,4,5,6-tetrachloropyrimidine allow a convenient synthesis of mono-, di-, tri- and tetraarylpyrimidines which are not readily available by other methods. All reactions proceed with excellent site-selectivity. [source] ChemInform Abstract: Synthesis of New Polysubstituted (Pyrazoles, Pyrimidines and Quinolines) Five- and Six-Membered Heterocycles: Reaction of ,,,-Dioxoketene Dithioacetals with Nucleophiles.CHEMINFORM, Issue 43 2010M. A. Ebraheem Abstract The method allows an easy access to the synthetically important N-heterocycles. [source] ChemInform Abstract: Efficient Access to Polysubstituted Amidines, Benzimidazoles and Pyrimidines from Amides.CHEMINFORM, Issue 23 2010Jing Wang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Synthesis, Analgesic and Antiinflammatory Activities Evaluation of Some Bi-, Tri- and Tetracyclic Condensed Pyrimidines.CHEMINFORM, Issue 9 2010Kamilia M. Amin Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Synthesis and Antiinflammatory Activity of 2-(2-Aroylaroxy)-4,6-dimethoxy Pyrimidines.CHEMINFORM, Issue 48 2008T. D. Venu Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] A Straightforward Preparation of Fluorine-Containing 1,2-Dihydropyrimidines and Pyrimidines with 2,2-Dihydropolyfluoroalkylaldehydes.CHEMINFORM, Issue 40 2007Xian-Jin Yang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Photochemical Synthesis of Polycyclic Pyrimidines Through the Acid Catalyzed Cycloaddition of 6-Chloro-1-methyluracil to Methyl Substituted Benzenes.CHEMINFORM, Issue 22 2007Kazue Ohkura Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Synthesis of Trisubstituted Pyrimidines by Regioselective SNAr and Suzuki Reactions of Polyhalopyrimidines.CHEMINFORM, Issue 31 2006Jonathan M. Large Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Viehe,s Salt in a Novel One Pot Synthesis of Pyrimidines.CHEMINFORM, Issue 23 2005Alexander S. Kiselyov Abstract For Abstract see ChemInform Abstract in Full Text. [source] N-Amination of Unsymmetrically Substituted Pyrimidines.CHEMINFORM, Issue 43 2003Synthesis of Isomeric N-Aminopyrimidones. Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: Preparation of 4,5-Disubstituted Pyrimidines: Ring Substitution of 5-Mesyloxymethylpyrimidines.CHEMINFORM, Issue 19 2001Howard Sard Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] DNA Containing Side Chains with Terminal Triple Bonds: Base-Pair Stability and Functionalization of Alkynylated Pyrimidines and 7-DeazapurinesCHEMISTRY & BIODIVERSITY, Issue 5 2006Frank Seela Abstract The synthesis of a series of oligonucleotides containing 5-substituted pyrimidines as well as 7-substituted 7-deazapurines bearing diyne groups with terminal triple bonds is reported. The modified nucleosides were prepared from the corresponding iodo nucleosides and diynes by the Sonogashira cross-coupling reaction. They were converted into phosphoramidites and employed in solid-phase synthesis of oligonucleotides. The effect of the diyne modifications on the duplex stability was investigated. The modified nucleosides were used for further functionalization using the protocol of Huisgen,Sharpless [2+3] cycloaddition (,click chemistry'). [source] Assessment of genotoxicity in rats treated with the antidiabetic agent, pioglitazoneENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2008Abdulkerim Bedir Abstract Pioglitazone (PIO), a member of the thiazolidinedione class of antidiabetic agents, specifically targets insulin resistance. Drugs of this class act as ligands for the gamma subtype of the peroxisome proliferator-activated receptor. Although troglitazone, another drug in this class, displayed unacceptable hepatotoxicity, PIO was approved for human use by the U.S. Food and Drug Administration. To our knowledge, there are no published reports on the genotoxicity of PIO; however, the package insert indicates that it has minimal genotoxicity. In this study, we used the comet assay to investigate the DNA damage in the peripheral blood and liver cells of rats treated with PIO. Sixteen male Sprague-Dawley rats were randomly distributed into four groups, and dosed daily for 14 days by oral gavage with 0, 10, 20, and 40 mg/kg/day PIO. A dose-dependent increase in DNA damage, as assessed by % tail DNA, was observed in both hepatocytes and blood lymphocytes of the PIO-treated groups, with significant increases detected between the rats treated with all the doses of PIO and the control, and between the rats treated with different PIO doses (P < 0.005 to P < 0.0001). Treating nuclei from the exposed animals with an enzyme cocktail containing Fpg and Endonuclease III prior to performing the comet assay increased the level of DNA damage, which reflects oxidized purine and pyrimidine. Taken together, our data indicate that PIO is able to dose-dependently induce DNA damage in both the liver and blood lymphocytes of rats, which is partially due to the generation of oxidative lesions. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] Mutation spectrum in UVB-exposed skin epidermis of Xpa -knockout mice: Frequent recovery of triplet mutationsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2007Hironobu Ikehata Abstract Knockout mutations in both alleles of the Xpa gene give rise to a complete deficiency in nucleotide excision repair (NER) in mammalian cells. We used transgenic mice harboring the ,-phage-based lacZ mutational reporter gene to study the effect of Xpa null mutation (Xpa,/,) on damage induction, repair, and mutagenesis in mouse skin epidermis after UVB irradiation. UVB induced equal amounts of cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (64PPs) in mouse skin epidermis of Xpa,/, and wild-type mice. Neither photolesion was removed in the Xpa,/, epidermis by 12 hr after irradiation whereas removal of 64PPs was observed in the epidermis of wild-type mice. Irradiation with 200 and 300 J/m2 UVB increased the lacZ mutant frequency in the epidermis of Xpa,/, mice, but the induced mutant frequencies were not significantly different from those previously determined for wild-type mice. One-hundred lacZ mutants isolated from the UVB-exposed epidermis of Xpa,/, mice were analyzed and compared with mutant sequences previously determined for irradiated wild-type mice. The distribution of the mutations along the lacZ transgene and the preferred dipyrimidine context of the UV-specific mutations were similar in mutants from the Xpa,/, and wild-type mice. The spectra of the mutations in the two genotypes were both highly UV-specific and similar in a dominance of C , T transitions at dipyrimidine sites; however, Xpa,/, mice had a higher frequency than wild-type mice of two-base tandem substitutions, including CC , TT mutations, three-base tandem mutations and double base substitutions that were separated by one unchanged base in a three-base sequence (alternating mutations). These tandem/alternating mutations included a remarkably large number of triplet mutations, a recently reported, novel type of UV-specific mutation, characterized by multiple base substitutions or frameshifts within a three-nucleotide sequence containing a dipyrimidine. We conclude that the triplet mutation is a UV-specific mutation that preferably occurs in NER-deficient genetic backgrounds. Environ. Mol. Mutagen., 2007. © 2006 Wiley-Liss, Inc. [source] Synthesis and Characterization of a New Guanidine,Borane Complex and a Dinuclear Boron(II) Hydride with Bridging Guanidinate LigandsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 28 2007Oxana Ciobanu Abstract We report the synthesis and structural characterization of the new monomeric borane complex H3B·hppH (hppH = 1,3,4,6,7,8-hexahydro-2H -pyrimido[1,2- a]pyrimidine), which represents the first example of a structurally characterized 1:1 complex between hppH and a group 13 element hydride. Significant intramolecular and, in the crystalline phase, intermolecular H···H contacts are established in this complex. It is shown that the complex can be used as a precursor to new dinuclear boron(II) compounds featuring a B,B single bond. Thus H2 elimination followed by dimerization of H3B·hppH leads to [(hpp)BH]2 with two bridging hpp units. The structural details derived from X-ray diffraction measurements are reported.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Kinetic and Equilibrium Studies of Reactions of N-Heterocycles with Dimeric and Monomeric Oxorhenium(V) ComplexesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 10 2003James H. Espenson Abstract Equilibrium constants have been evaluated for the reaction {MeReO(edt)}2 + 2 L , 2 MeReO(edt)L, where edt is 1,2-ethanedithiolate and L is any of 13 N-donor heterocyclic ligands. The values of K range from 1.37(27)×10,2 for pyrimidine to 1.95(6)×106 for imidazole at 25 °C in chloroform. A successful correlation of logK with log (Ka) of HL+ was realized except in the case of the 2-substituted ligands 2-picoline and quinoline, where steric effects make K smaller than expected from the proton basicity of L. The kinetics of the same reactions were studied; the rate law for the reaction in the forward direction is given by ,d[{MeReO(edt)}2]/dt = {ka + kb[L]}[L] × [{MeReO(edt)}2]. Except for 2-picoline and quinoline, the major pathway is provided by the term that shows the quadratic dependence on [L]. Values of log (kb) also correlate with log K, and therefore necessarily with log (Ka). [source] Application of Selective Palladium-Mediated Functionalization of the Pyrido[3,,2,:4,5]pyrrolo[1,2- c]pyrimidine Heterocyclic System for the Total Synthesis of Variolin B and Deoxyvariolin B,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 29 2010Alejandro Baeza Abstract The reaction of protected 3-bromo-2-(bromomethyl)-4-methoxypyrrolo[2,3- b]pyridine and tosylmethyl isocyanide (TosMIC) afforded a pyrido[3,,2,:4,5]pyrrolo[1,2- c]pyrimidine derivative in good yield. This compound was transformed through installation of the pyrimidine moiety in the C5 position, hydrolysis, and decarboxylation in an advanced intermediate for the total or formal synthesis of the naturalalkaloid variolin B. Reaction of 3-bromo-2-(bromomethyl)-4-chloropyrrolo[2,3- b]pyridine with N -tosylmethyl dichloroformimide as a synthetic TosMIC equivalent afforded trihalo-substituted pyrido[3,,2,:4,5]pyrrolo[1,2- c]pyrimidine. This compound was used in a new total synthesis of the alkaloid variolin B by selective and sequential C,N, C,C, and C,O palladium-mediated functionalization at the C9, C5, and C4 positions of the pyrido[3,,2,:4,5]pyrrolo[1,2- c]pyrimidine system. A formal synthesis of deoxyvariolin B is also described by using the same synthetic strategy. [source] Syntheses of Triostin A Antibiotic and Nucleobase-Functionalized Analogs as New DNA BindersEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 28 2009Anmol Kumar Ray Abstract A total synthesis of the natural product triostin A, wherein the N -methylated depsipeptide scaffold is constructed by solution-phase peptide chemistry followed by disulfide formation and macrocyclization, is described. Finally, the quinoxalines were attached to provide the DNA bisintercalator. Analogs of triostin A were obtained by the successive functionalization of the cyclic depsipeptide with pyrimidine or purine recognition units. The attachment of functional units was achieved by the orthogonal protection of the respective side chain amino functionalities. The nucleobase-functionalized triostin analogs have the potential to recognize double-stranded DNA by hydrogen bonding. The interaction with DNA was investigated by UV spectroscopy and fluorescence intercalator displacement. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Efficient Routes to Acenaphthylene-Fused Polycyclic Arenes/Heteroarenes and Heterocyclic Fluoranthene AnaloguesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2005Kausik Panda Abstract The acenaphthenone-derived , -oxoketene dithioacetal 2 has been subjected to various [3 + 3] aromatic and heteroaromatic annulation and other heterocyclization reactions previously developed in our laboratory, providing short and efficient routes to a diverse range of known and unknown acenaphtho-annulated linear and angular PAHs, heteroaromatics and five-membered heterocycles in good yields. Thus, benzo- and naphthoannulation of 2 with various allyl and benzyl Grignard reagents afforded substituted fluoranthenes 4a,c and benzo[k]fluoranthene 8, respectively, in good yields. Similarly, the parent benzo[j]fluoranthene 15a and its substituted derivative 16b have been synthesized by base-induced conjugate 1,4-addition of arylacetonitriles to 2, followed by acid-induced cyclization of the conjugate adducts 12a,b to give 13a,b and subsequent further transformations. The adducts obtained by 1,4-addition of anions derived from acetophenone and acenaphthenone were subjected toheterocyclization in the presence of ammonium acetate to give 8-arylacenaphtho[1,2- b]pyridines 18a,b and bis(acenaphtho)-annulated pyridine 20. Heterocyclization of 2 with bifunctional nucleophiles such as 2-picolyllithium and guanidinium nitrate afforded the corresponding acenaphtho[1,2- b]quinolizinium salt 23 and acenaphtho[1,2- d]pyrimidine 24, respectively, in high yields. Finally, acenaphtho[1,2- c]-fused five-membered heterocycles such as 7-(methylthio)acenaphtho[1,2- c]thiophene (25), 7-(methylthio)acenaphtho[1,2- c]furan (27) and 7-(methylthio)acenaphtho[1,2- c]pyrrole-2-carboxylic acid (30) were obtained in good yields by subjection of 2 to Simmons,Smith reaction conditions or by treatment with dimethylsulfonium methylide or glycinate dianion. Some of these newly synthesized PAHs or fused heterocycles were subjected to Raney Ni desulfurization to furnish sulfur-free compounds. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Brominated 4-(Trifluoromethyl)pyrimidines: A Convenient Access to Versatile IntermediatesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 20 2004Levente Ondi An expedient route to all three monobrominated and all three dibrominated isomers of 4-(trifluoromethyl)pyrimidine, and to several other halogenated pyrimidines, is described. Key steps are the electrophilic introduction of the halogen in the 5-position of 2- or 4-pyrimidinones, the bromodeoxygenation of pyrimidinones or thiopyrimidinones using phosphorus tribromide, and the partial debromination of dibromo-4-(trifluoromethyl)pyrimidines. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Inhibition of urokinase receptor gene expression and cell invasion by anti-uPAR DNAzymes in osteosarcoma cellsFEBS JOURNAL, Issue 14 2005Charles E. De Bock The urokinase-type plasminogen activator (uPA) receptor (uPAR) has been implicated in signal transduction and biological processes including cancer metastasis, angiogenesis, cell migration, and wound healing. It is a specific cell surface receptor for its ligand uPA, which catalyzes the formation of plasmin from plasminogen, thereby activating the proteolytic cascade that contributes to the breakdown of extracellular matrix, a key step in cancer metastasis. We have synthesized three different DNA enzymes (Dz372, Dz483 and Dz720) targeting uPAR mRNA at three separate purine (A or G),pyrimidine (U or C) junctions. Two of these DNAzymes, Dz483 and Dz720, cleaved uPAR transcript in vitro with high efficacy and specificity at a molar ratio (uPAR to Dz) as low as 1 : 0.2. When analyzed over 2 h with a 200-fold molar excess of DNAzymes to uPAR transcript, Dz720 and Dz483 were able to decrease uPAR transcript in vitro by ,,93% and ,,84%, respectively. They also showed an ability to cleave uPAR mRNA in the human osteosarcoma cell line Saos-2 after transfection. The DNAzyme Dz720 decreased uPAR mRNA within 4 h of transfection, and inhibited uPAR protein concentrations by 55% in Saos-2 cells. The decrease in uPAR mRNA and protein concentrations caused by Dz720 significantly suppressed Saos-2 cell invasion as assessed by an in vitro Matrigel assay. The use of DNAzyme methodology adds a new potential clinical agent for decreasing uPAR mRNA expression and inhibiting cancer invasion and metastasis. [source] Replacement of Canonical DNA Nucleobases by Benzotriazole and 1,2,3-Triazolo[4,5- d]pyrimidine: Synthesis, Fluorescence, and Ambiguous Base PairingHELVETICA CHIMICA ACTA, Issue 4 2005Frank Seela The syntheses and the fluorescence properties of 7H -3,6-dihydro-1,2,3-triazolo[4,5- d]pyrimidin-7-one 2,-deoxy- , - D -ribonucleosides (=2,-deoxy-8-azainosine) 3 (N3), 15 (N2), and 16 (N1) as well as of 1,2,3-benzotriazole 2,- O -methyl- , - or - , - D -ribofuranosides 6 (N1) and 24 (N1) are described. Also the fluorescence properties of 1,2,3-benzotriazole 2,-deoxy- , - D -ribofuranosides 4 (N1) and 5 (N2) are evaluated. From the nucleosides 3,6, the phosphoramidites 19, 26a, 26b, and 28 are prepared and employed in solid-phase oligonucleotide synthesis. In 12-mer DNA duplexes, compound 3 shows similar ambiguous base-pairing properties as 2,-deoxyinosine (1), while the nucleosides 4,6 show strong pairing with each other and discriminate very little the four canonical DNA constituents. [source] | ||||||||||||||||||||||||||||||||||||||||