Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes.

Radioprotective effects produced by the condensation of plasmid DNA with avidin and biotinylated gold nanoparticles.

The treatment of aqueous solutions of plasmid DNA with the protein avidin results in significant changes in physical, chemical, and biochemical properties. These effects include increased light scattering, formation of micron-sized particles containing both DNA and protein, and plasmid protection against thermal denaturation, radical attack, and nuclease digestion. All of these changes are consistent with condensation of the plasmid by avidin.

DNA Binding Hydroxyl Radical Probes.

The hydroxyl radical is the primary mediator of DNA damage by the indirect effect of ionizing radiation. It is a powerful oxidizing agent produced by the radiolysis of water and is responsible for a significant fraction of the DNA damage associated with ionizing radiation. There is therefore an interest in the development of sensitive assays for its detection.

Free terminal amines in DNA-binding peptides alter the product distribution from guanine radicals produced by single electron oxidation.

Purpose: Electron deficient guanine radical species are major intermediates produced in DNA by the direct effect of ionizing irradiation. There is evidence that they react with amine groups in closely bound ligands to form covalent crosslinks. Crosslink formation is very poorly characterized in terms of quantitative rate and yield data.

Modeling the influence of histone proteins on the sensitivity of DNA to ionizing radiation.

The DNA-binding proteins that are present in chromatin significantly affect the sensitivity of cells to ionizing radiation and to the radiation chemistry of DNA damage. The interaction between protein and DNA modifies the radiation chemistry of the latter. To model these processes, we have examined the effects of ionizing radiation on the minichromosome form of SV40 (which contains histone proteins arranged in nucleosomes) and also on plasmid DNA in the presence of lysozyme.

Damage clusters after gamma irradiation of a nanoparticulate plasmid DNA peptide condensate.

We have gamma-irradiated plasmid DNA in aqueous solution in the presence of submillimolar concentrations of the ligand tetra-arginine. Depending upon the ionic strength, under these conditions, the plasmid can adopt a highly compacted and aggregated form which attenuates by some two orders of magnitude the yield of damage produced by the indirect effect. The yields of DNA single- and double-strand breaks (SSB and DSB) which result are closely comparable with those produced in living cells.

Characterization of a lipophilic plasmid DNA condensate formed with a cationic peptide fatty acid conjugate.

In the presence of cationic ligands, DNA molecules can become aggregated into larger particles in a process known as condensation. DNA condensates are of interest as models for the dense packing found in naturally occurring structures such as phage heads and chromatin. They have found extensive application in DNA transfection and also provide convenient models with which to study DNA damage by the direct effect of ionizing radiation.