Nucleic shifts 413

The most commonly used dye in fluorescence studies on nucleic acids is ethidium bromide. The dye has broad excitation bands centered around 280 and 460 nm and a strong emission around 600 nm. When the dye hinds to DNA by an intercalative mechanism, its emission is greatly enhanced and slightly shifted in wavelength. In the simplest case with ethidium bromide saturating intercalating sites,... 

Finally, we should note that a particularly important area of application where density functional techniques, in spite of the deficiencies noted above, are virtually without competition is provided by biochemically relevant molecules, such as enzymes or nucleic acids. The techniques discussed in this section are virtually the only quantum chemical methods which can be applied in this context due to their outstanding price/performance ratio. For example, the 13C and 15N chemical shifts in bacteriochlorophyll A have been studied by Facelli, 1998, and in another investigation the 57Fe, 13C and 170 shifts in iron porphyrin derivatives gave important clues as to the structural details of these species, as shown by McMahon et al 1998. 

A simple NMR technique, and arguably the most widely used and effective for hit validation, is the chemical shift perturbation method. In this approach, a reference spectrum of isotopically labeled target is recorded in absence and presence of a given test ligand (or a mixture of test ligands). Commonly, differences in chemical shift between free and bound protein target are observed in 2D [15N, 1H and/or 2D [13C, H] correlation spectra of a protein (or nucleic acid) upon titration of a ligand... 

Overall, the significant Stokes shift of 100 nm and the good quantum yields make the coumarin dye a powerful fluorescent probe for nucleic acids assays or cell biology. The postsynthetic click chemistry makes this fluorophore readily accessible for fluorescent labeling of nucleic acids. 

The shift towards viewing nucleic acids as the genetic material begins with the critical paper by Avery et at. (1944). 

Case58 investigated the effect of ring currents on NMR shielding constants by means of the DFT calculations. The studied rings included the ones commonly found in proteins and nucleic acids. The shielding constants were calculated for methane molecule placed in several positions relative to the ring. The calculations provided data needed to derive structural parameters from measured chemical shifts in proteins and nucleic acids. 

Fig. 16.6 Estimates of device performance in response to nucleic acid binding, (a) FDTD simulation showing the mass sensitivity of the device plotted as a function of the number of functionalized holes. The circles indicate the sensitivity values calculated from the simulations. The solid curve shows a least squares fit using an analytical model for the device sensitivity, which is described below, (b) Plot illustrating the dependence of the shift in resonant wavelength of a resonator on the number of functionalized holes. The blue circles indicate the data obtained from 3D FDTD simulations. The solid curve is a best fit curve of the form a( 1 eTbN) where a and b are arbitrary constants. The values of a and b used here are 6.159 nm and 0.4273, respectively. Reprinted from Ref. 37 with permission. 2008 Optical Society of America...

Tab. 6.1 Calculated and experimental solid-state principle values of the chemical shifts of selected nitrogen atoms in nucleic acid bases...

Tab. 6.2 Calculated principle values nucleic acid bases and base pairs and orientations of chemical shift tensors of the imino nitrogens in...

A number of animal studies have revealed extrapulmonaiy effects. Again, there is some question as to which of these may represent an effect of ozone, or a direct ozone-induced intermediate, rather than a more indirect response to pulmonary toxicity, perhaps mediated by neurohumoral factors. Thus, for instance, the observations of altered hepatic nucleic acid concentrations, shifts in the content of metals in the liver, alterations in urinary pH, increases in liver weight and alkaline phosphatase... 

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