113 resultados para QUADRUPLEX


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The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to directly inhibit telomerase activity. The reactivation of this enzyme in immortalized and most cancer cells suggests that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. In this paper, we describe ethidium derivatives that stabilize G-quadruplexes. These molecules were shown to increase the melting temperature of an intramolecular quadruplex structure, as shown by fluorescence and absorbance measurements, and to facilitate the formation of intermolecular quadruplex structures. In addition, these molecules may be used to reveal the formation of multi-stranded DNA structures by standard fluorescence imaging, and therefore become fluorescent probes of quadruplex structures. This recognition was associated with telomerase inhibition in vitro: these derivatives showed a potent anti-telomerase activity, with IC50 values of 18–100 nM in a standard TRAP assay.

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DNA fragments with stretches of cytosine residues can fold into four-stranded structures in which two parallel duplexes, held together by hemiprotonated cytosine.cytosine+ (C.C+) base pairs, intercalate into each other with opposite polarity. The structural details of this intercalated DNA quadruplex have been assessed by solution NMR and single crystal x-ray diffraction studies of cytosine-rich sequences, including those present in metazoan telomeres. A conserved feature of these structures is the absence of stabilizing stacking interactions between the aromatic ring systems of adjacent C.C+ base pairs from intercalated duplexes. Effective stacking involves only the exocyclic keto groups and amino groups of the cytidine bases. The apparent absence of stability provided by stacking interactions between the bases in this intercalated DNA has prompted us to examine the available structures in detail, in particular with regard to unusual features that could compensate for the lack of base stacking. In addition to base-on-deoxyribose stacking and intra-cytidine C-H...O hydrogen bonds, this analysis reveals the presence of a hitherto unobserved, systematic intermolecular C-H...O hydrogen bonding network between the deoxyribose sugar moieties of antiparallel backbones in the four-stranded molecule.

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Isolated guanine quadruplex structures have been described at high resolution both in solution and in the solid state. The existence of this unusual DNA structure in vivo and its biological significance remain to be determined. We describe the binding of 3,3'-diethyloxadicarbocyanine to dimeric hairpin guanine quadruplexes. This interaction results in a set of unique spectrophotometric signatures, none of which arises from binding to single strands or Watson-Crick duplexes. These unique signatures include a new absorbance peak (lambda max = 534 nm), an induced circular dichroism (lambda = 534-626 nm), a quenching of the dye fluorescence upon excitation with visible light, and strong energy transfer from DNA. This last effect provides the basis for detecting hairpin quadruplex structures in the presence of excess amounts of nonquadruplex DNA structures, such as single strands and Watson-Crick duplexes. The mechanism of quadruplex recognition by this dye is discussed, along with the possibility of using this dye as a probe for hairpin quadruplex structures in vitro and in vivo.

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Contiene: Index omnium diui Hieronymi lucubrationum ... ; Opus epistolarum diui Hieronymi ... [T. 1] ; Alter tomus Epistolarum diui Hieronymi ... [T. 2] ; Tomus tertius Epistolarum siue librorum epistolarium diui Eusebij Hieronymi ... [T. 3] ; Tomus quartus in cuius prima parte reperies ... falso inscripta Hieronymo ..., in secunda ... titulis autorem testantia, in tertia lectu prorsus ... atributa doctis uiris [T. 4] ; Quintus tomus Operum diui Hieronymi Commentarios in prophetas, quos maiores uocant ... continent [T. 5] ; Sextus tomus Operum diui Hieronymi Commentarios in duodecim prophetas, quos minores uocant ... continet [T. 6] ; Septimo tomo haec insunt in parabolas Salomonis commentarij, in Ecclesiasten diui Hieronymi ... commentarij ... [T. 7] ; Octauus tomus Commentarios in Psalterium habet ... [T. 8] ; Tomus nonus Operum diui Hieronymi Eusebii ..., postremo Didymi de Spiritusancto librum a Hieronymo uersum [T. 9] ; Appendici huic inest quadruplex psalterium uidelicet hebraeum [et] hebraica ueritas diuo Hieronymo interprete, graecum [et] aeditio ultima latina autore incerto.

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The present invention relates to a logic gate, comprising a metamaterial surface enhanced Raman scattering (MetaSERS) sensor, comprising (a) alphabetical metamaterials in the form of split ring resonators operating in the wavelength range of from 560 to 2200 nm; and (b) a guanine (G) and thymine (T)-rich oligonucleotide that can, upon presence of potassium cations (K+), fold into a G-quadruplex structure, and in presence of Hg2+, form a T-Hg2+-T hairpin complex that inhibits or disrupts the G-quadruplex structure formed in presence of K+, as well as methods of operating and using such a logic gate.