Destabilization of the double helix

Numerous studies, carried out to determine how ligation of platinum affects the conformation and stability of normal B-DNA, revealed significant destabilization of the double helix (reviewed in [5] see also [6]). More detailed information has been provided by recent structural analyses of the... 

Experimental investigations were mainly convened with metals of group VIII, namely Fe " ", Co, and Ni " ". These metals form covalent bonds with the N atoms of DNA, producing pronounced destabilization of the double helix with harmful biological consequences. 

Jackson BA, Barton JK. Recognition of base mismatches in DNA by 5,6-chrysenequinone diimine complexes of rhodium(III) A proposed mechanism for preferential binding in destabilized region of the double helix. Biochemistry 2000 39 6176-82. 

The diameter of the double helix is 2.4 nm. Note that the interior space of the double helix is only suitable for base pairing a purine and a pyrimidine. Pairing two pyrimidines would create a gap, and pairing purines would destabilize the helix. 

The double helix is somewhat destabilized after the platination, as reflected by the decrease of the melting temperature of the duplex by 10-20°C at NMR concentrations (3 mM). 

Application of Equation 17 to the two systems discussed here shows that dissolution of / -lactoglobulin in 40% 2-chloroethanol in the final conformation assumed by the protein in this medium stabilizes the system since (d/x2(e)/dm3) = —6,000 cal/mole protein/mole 2-chloroethanol in 1000 grams of water. This means that in this system the protein has a stronger affinity for the alcohol than for water relative to the bulk solvent composition. As a result, excess alcohol is found in the domain of the protein. Exactly the opposite is true for the DNA in salt system. Here, the obtained values of D result in a destabilization of the system by the salt since (dfi2ie /dm3) = 50-100 cal/(mole/A) of DNA per mole of salt in 1000 grams of water. For a double helix of 100 base pairs this amounts to a destabilization of the order of 10 kcal/mole of salt added. As pointed out above, this results in excess water in the domain of the macromolecule —i.e.9 in preferential hydration of the DNA. 

The double helix is somewhat destabilized, compared with the unplatinated duplex, as seen from the decrease in melting temperature of about 10-20°. 

The pKa for the proton on N -1 of guanine is typically 9.7. When the pH approaches this value, the proton on N-1 is lost (see Figure 1.16). Because this proton participates in an important hydrogen bond, its loss substantially destabilizes the DNA double helix. The DNA double helix is also destabilized by low pH. Below pH 5, some of the hydrogen bond acceptors that participate in base-pairing become protonated. In their protonated forms, these bases can no longer form hydrogen bonds and the double helix separates. Thus, acid—base reactions that remove or donate protons at specific positions on the DNA bases can disrupt the double helix. 

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