CHED 106

DNA interstrand cross-linking by a diepoxide mycotoxin

Jacob E. Conklin and Julie T. Millard. Department of Chemistry, Colby College, 5750 Colby College, Waterville, ME 04901, fax: 207-872-3804, jeconkli@colby.edu

Diepoxides are widespread in nature and act as cellular cross-linkers, leading to chromosomal aberrations and the induction of cancer. Repandiol, a diyne diol diepoxide, was isolated from the edible mushroom Hydnum repandum by Takahashi, Endo, and Nozoe in 1992 and reported to display potent cytotoxic activity, attributed to its bifunctional alkylating capacity. We have purified repandiol for DNA interstrand cross-linking studies using defined sequence DNA oligomers. Preliminary results suggest that repandiol is a much less efficient DNA cross-linker than the chemically simplest diepoxide, diepoxybutane. However, like the diepoxyalkanes previously studied in our laboratory, repandiol shows a preference for alkylation at guanine residues.