Abstract
The sequence specificity of bizelesin, an interstrand DNA-DNA cross-linker related to the monoalkylating compound (+)-CC-1065, was studied using restriction enzyme fragments. Bizelesin, like (+)-CC-1065, forms monoalkylation adducts through N3 of adenine but can also form DNA-DNA cross-links six base pairs apart on opposite strands. Compared to many other minor groove cross-linking compounds, bizelesin is very efficient at cross-linking DNA. There is a higher than expected proportion of cross-linked adducts based upon the relative number of cross-linked vs monoalkylated adducts. This is rationalized based upon the relative thermodynamic stability of the cross-linked vs monoalkylated species
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