Correlation function, nucleic acids

The method is likely to be useful for the numerical calculation of other correlation functions of importance to complex molecules. An example is the orientation correlation functions of interest in NMR-derived dynamical estimates for proteins and nucleic acids [134], Such correlations are difficult to converge numerically when multiple conformations separated by large free energy barriers contribute to their measurement. 

Other systems like electroporation have no lipids that might help in membrane sealing or fusion for direct transfer of the nucleic acid across membranes they have to generate transient pores, a process where efficiency is usually directly correlated with membrane destruction and cytotoxicity. Alternatively, like for the majority of polymer-based polyplexes, cellular uptake proceeds by clathrin- or caveolin-dependent and related endocytic pathways [152-156]. The polyplexes end up inside endosomes, and the membrane disruption happens in intracellular vesicles. It is noteworthy that several observed uptake processes may not be functional in delivery of bioactive material. Subsequent intracellular obstacles may render a specific pathway into a dead end [151, 154, 156]. With time, endosomal vesicles become slightly acidic (pH 5-6) and finally fuse with and mature into lysosomes. Therefore, polyplexes have to escape into the cytosol to avoid the nucleic acid-degrading lysosomal environment, and to deliver the therapeutic nucleic acid to the active site. Either the carrier polymer or a conjugated endosomolytic domain has to mediate this process [157], which involves local lipid membrane perturbation. Such a lipid membrane interaction could be a toxic event if occurring at the cell surface or mitochondrial membrane. Thus, polymers that show an endosome-specific membrane activity are favorable. 

Discussion in this section is confined to the matter mentioned in the introduction, which has provided such a fresh and energetic impetus to this whole subject, namely the direct and quantitative correlation between the amounts of several specific and identifiable photoproducts formed in the photolysis of nucleic acids and the amount of inactivation of the nucleic acid biological function. This specific area, however, is one which has drawn much attention, and to which several of the recent reviews are devoted.8,10,113"90 There is little need to extend these excellent articles, and so a comprehensive survey of the literature will not be attempted here, but merely a summary and interpretation. 

Recent developments in the direct observation of J couplings across hydrogen bonds in proteins and nucleic acids provide additional information for structure and function studies of these molecules by NMR spectroscopy. Yan et al proposed a modified J(N,N)-correlated TROSY experiment... 

CW EPR spectroscopy is extensively used to probe local and global dynamics of nucleic acid molecules and to correlate these data with NA structures and functional aspects. This is particularly useful to investigate and monitor NA-protein or NA-ligand interactions. In the following we are going to highlight some recent applications of CW EPR to study RNA and DNA molecules. 

Nucleic acids > ca. 10 bp long are not spherically symmetric. To a good approximation they are equivalent to circular cylinders with a hydrodynamic diameter of 20-23 A for DNA (33-35) and 25 A for RNA (35). The correlation function for such symmetric top molecules consist of three exponentials, whose arguments are combinations only of the correlation time for end over end tumbling (tl) and for rotation about the principal symmetiy axis (ts). Thus for anisotropic motion, two independent correlation times are needed to describe the rotational diffusion. The spectral density function also depends on the angle (0) the interproton vector makes with the principal axis. J(0), and hence the cross-relaxation rate constant, varies as a function of this angle according to (.16) ... 

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