Strange, Richard William (1985) A spin-label ESR study of drug binding to DNA. Doctoral thesis, Keele University.

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Abstract

A spin-labelled derivative of the drug Proflavine was prepared and its interactions with natural DNA in fibres were investigated using the technique of electron spin resonance (ESR). Computer simulations of the ESR spectra showed that spin-labelled proflavine adopts a preferred orientation in each of the different DNA conformations. In A- and C-form DNA the binding geometry is explained by an external interaction between the drug molecules and the phosphate groups of the double helix. In B-form DNA the drug molecules exhibited some form of rotational motion. Simulations indicated that this motion was directed about the helix axis, a conclusion which is consistent with an intercalative mode of binding. An examination of the B-form X-ray diffraction patterns confirmed that intercalation had occurred.
A difference was observed in the binding of the drug to different species of DNA, suggesting that some form of site specific interaction is involved. The importance of drug concentration on the conformational properties of DNA was recognised.
The binding of several Phenothiazine tranquilisers to DNA was also investigated. The solution ESR spectra of these (oxidised) drug molecules showed that the distribution of unpaired spin density over the heterocyclic ring depends upon the substituted groups present. However, in DNA fibres the different drug species adopted the same binding geometry. Although the ESR results were consistent with both intercalation and external binding, the large spread of drug orientations estimated from computer simulations suggests that external binding is more likely.
DNA from the bacteriophage dW-14 was spin-labelled in order to determine the conformation of the putrescine groups attached to the thymine bases. The information obtained from these experiments suggests that the putrescine groups project into the major groove in B- and C-form DNA, whereas in the A-conformation they lie close to each other in the hollow interior of the helix.

Item Type: Thesis (Doctoral)
Subjects: Q Science > QC Physics
Divisions: Faculty of Natural Sciences > School of Chemical and Physical Sciences
Contributors: Slade, EF (Thesis advisor)
Depositing User: Lisa Bailey
Date Deposited: 13 Dec 2019 11:59
Last Modified: 13 Dec 2019 11:59
URI: https://eprints.keele.ac.uk/id/eprint/7401

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