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Title: Studies of the use of derivatised polycations as potential drug delivery systems to DNA
Author: Besley, Stephen C.
ISNI:       0000 0001 3462 3802
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1991
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The major target of ionising radiation has been determined as cellular DNA. Damage to DNA, as detected at 77K under conditions of direct damage by ESR, is localised on the bases thymine and guanine. This damage leads to single and double strand breaks, precursors of cell death and mutagenesis. In an attempt to intercept the damage at the bases, before formation of strand breaks, the use of polycations as potential drug delivery systems to DNA has been examined. Magnetic resonance techniques have been used to establish that polyamines used are present almost completely as polyammonium cations at pH 7 and to probe the interactions of a number of polycations with DNA. Sodium-NMR was used to investigate the affinity of polyamines, poly- aminothiols and transition-metal complexes for DNA, via sodium ion displacement from the DNA region. It was found that small metal complexes displace a greater number of sodium ions than polyamines of similar charge. Application of the counterion condensation theory led to a model of the counterions existing within a cylinder around the DNA of approximate radius 20A. The mode of interaction of polyammonium cations was studied using proton magnetic resonance. Linewidths, related to the transverse relaxation rate, give information on the motion of compounds close to DNA. Comparison of linewidths in the presence and absence of DNA revealed no significant broadening. This was interpreted as indicative of a loose, electrostatic interaction, not significantly hindering motion of the cations close to DNA, suggesting rapid motion of polyammonium ions along the DNA. The radioprotection of DNA by various transition-metal complexes was studied using ESR. Certain compounds exhibited protection via electron transfer, resulting in a decreased radical yield.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Radiation-induced cell damage