DNA-Ligand Interactions

DNA can interact with proteins, drugs, carcinogens, mutagens and dyes, according to different modes of binding [21]. 

All these factors induce external molecules to interact in varioiB fashions with DNA. The different interaction modes , commonly considered in the literature, are surface binding in the major or minor groove, intercalation, and external binding in the atmosphere of ions of the DNA polyelectrolyte (Fig. 5). 

If the ligand has an aromatic portion (normally corresponding at least to three fused six-membered rings), it can position itself between base-pairs, in 

Schematic representation of the surface binding, intercalation, and externa] binding in the atmosphere of ions around the DNA for small molecules 

The external binding mode (Fig. 5) is due mostly to the electrostatic interaction of cations with the negatively charged phosphate backbone at the periphery of the double helix [33]. 

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Shafer RH, Brown SC (1988) In Kallenbach NR (ed) Chemistry and physics of DNA-ligand interactions. Adenine Pre Schenectady, NY, p 109... 

In this section, we describe the application of the GBPM method to different selected complexes. The resulting pharmacophore models have been tested extensively for their capacity to retrieve known ligands for the target. The application examples were selected to be representative of a certain type of molecular interaction, including protein-protein, and DNA-ligand interactions. More application examples will be described elsewhere [13]. 

Kennard O (1987) DNA structure. Current results from single crystal X-ray diffraction studies. In Guschlbauer W, Saenger W (eds) DNA ligand interactions from drugs to proteins. Plenum Press, New York, pp 1-22... 

The Scatchard plots for the binding of tilorone to calf thymus DNA (Fig. 4a), Mic. lys. DNA (Fig. 4b), poly (dA-dT) -poly (dA-dT) (Fig. 4c), and poly (dG-dC) poly (dG-dC) (Fig. 4d) are shown in Fig. 4. As follows from the Scatchard plots for natural DNAs, (Fig. 4a and 4b), the independent site model does not fit for DNA-ligand interaction however, we employed the binding parameters of this model to analyse the Scatchard plots. The binding parameters, Kapp and Bapp derived from the Scatchard plots (Fig. 4a-d) are presented in Table 1. This table summarizes the results of several measurements. 

Figure 3 DNA-ligand interactions intercalation and groove binding...

W. Guschlbauer and W. Saenger, DNA-Ligand Interactions From Drugs to Proteins (Plenum, New York, 1987). 

In future work, the methods illustrated in this paper will be applied to a variety of problems in macromolecular kinetics. More detailed studies of substrate binding to superoxide dismutase and antigen binding to antibody molecules are in progress. Other studies that are planned or in progress include the examination of Coulombic contributions to polymer growth and to DNA-ligand interactions. 

An increase in optical thickness of the thin film, caused by e.g. ligand adsorption, will shift the interference spectrum to a higher wavelength and widen the distance between the minima and maxima in the inteference spectra as illustrated in Fig. 14.45b. This is the principle behind reflectometric interference spectroscopy, or Rifs [315]. Due to the high sensitivivity of the detection (ppm levels of phase shifts can be measured [316]), the RIfS device has been successfully used for the study of various biological interactions at surfaces, such as mouse anti-atrazine/ atrazine [317] and DNA-ligand interactions [318]. The principle of RIfS also allows the construction of low-cost devices. 

The above-mentioned results may be alternatively described in terms of the one dimensioned Ising model in order to extract the feature of the interactions. There are several theories that treat DNA-ligand interactions, but one of the simplest was conveniently chosen to express cooperative nature of the phenomena. The phosphate groups on DNA u e viewed as an array of binding sites along the poly(nucleotide) helices, each site being occupied or vacant. The partition function, z, for such system is written as. 

Murat P, Singh Y, Defrancq E (2011) Methods for investigating G-quadruplex DNA/ligand interactions. Chem Soc Rev 40 5293-307... 

Kupferschmitt, G., Schmidt, J., Schmidt, Th., Fera, B., Buck, F, and Riiterjans, H (1987) N labeling of oligodeoxynucleotides for NMR studies of DNA-ligand interactions Nucl Acids Res 15,6225-6241... 

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