Currently, there has been considerable interest in the mechanisms associated with radical-induced DNA cleavage. Apart from the established intermediacy of radicals in the C4' and C-5' positions of the sugar backbone, there has been substantial experimental evidence that C-l' radicals are also intermediates in the reaction between neocarzinostatin and double stranded DNA containing dAGC sequences and also in the reaction of bleomycin with oligonucleotides modified with a single ribo or arabino nucleoside. The goals of the proposed research will be to prepare a number of modified nucleosides and oligonucleotides, with modifications that can generate specifically a single C-1' radical species and study its degradation under a variety of condiiions. Moreover, we plan to design a second set of modifications which can specifically trap an in vitro generated C-1' radical species, this being either a carbon centered or oxygen radical.
Fields of science
Call for proposalData not available
Funding SchemeRGI - Research grants (individual fellowships)
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