Theoretical and Experimental Characterization of Polyamine/DNA Interactions
For several years, work in our laboratory has been directed toward an understanding of the interactions of polyamines and nucleic acids. The initial impetus to this research was the finding that the cytotoxicity of antineoplastic agents such as cis-platinum and the 2-chloroethylnitrosoureas are altered in tumor cells in which intracellular levels of polyamines had been depleted by pretreatment with α-difluoromethylornithine (1, 2). It is thought that these agents kill cells by forming DNA interstrand crosslinks that prevent replication and lead to cell death. One possible explanation for the effects of polyamine depletion on cytotoxicity is that the conformation of intracellular DNA is altered, which would affect the mechanism of crosslink formation.
KeywordsMinor Groove Major Groove Phosphate Backbone Amino Proton Helical Axis
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