Intercalation, helix conformation changes

Intercalators have generally high DNA-binding constants (partition coefficients), and therefore after the interaction between intercalator compound and double helix, a conformational change occurs onto DNA that gives a very favorable free energy of complex formation [14], On the other hand, in bis-intercalators, for example, Echinomycin, two intercalative interactions perform via covalent bonds between aromatic rings of the molecule and DNA [14]. 

The DNA helix needs to imdergo significant conformational changes in order to accommodate an intercalator. Since in B-form DNA the nucleic bases are in close contact due to tt-stacking, they need to be separated from each other before an aromatic compoimd may intercalate between these base pairs. In general, the required space for a planar aromatic compoimd is approximately 3.4 A, which corresponds to the average thickness of aromatic molecules. 

The effects of intercalators (see also p. 262) are illustrated here using the example of the daunomycin-DNA complex, in which two daunomycin molecules (red) are inserted in the double helix (blue). The antibiotic s ring system inserts itself between G/C base pairs (bottom), while the sugar moiety occupies the minor groove in the DNA (above). This leads to a localized change of the DNA conformation that prevents replication and transcription. 

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