Date of Award


Document Type

Honors Thesis (Colby Access Only)


Colby College. Chemistry Dept.


Julie T. Millard

Second Advisor

Paul G. Greenwood

Third Advisor

Shari U. Dunham


The diepaxyalkanes, a family of DNA damaging agents, exhibit a lower crosslinking efficiency than the nitrogen mustards, despite sharing the same 5'-GNC target sequence for interstrand cross-linking. The cross-linking agents used in this study were diepoxybutane, diepoxyoctane and the nitrogen mustard, mechlorethamine. The main goal in the project was to understand the factors involved in the cross-linking yields of these agents. We used polyacrylamide gel electrophoresis (PAGE), denaturing PAGE, aqueous piperidine cleavage and phosphorimagery to study how flanking sequences around the core 5'-ONC target impact the cross-linking efficiency of diepoxyalkanes relative to mustards. Different synthetic DNA oligomer duplexes containing the sequence [NIGN2CN3Jcontaining each of the four possible bases for N1, N2, and N3 were used. The preliminary data indicated that there may be a preference far thymine as the N] base for diepoxybutane and mechlorethamine, while diepoxyoctane showed a preference for guanine as the N1 base in the core target sequence. This suggests that the flanking sequences may have an effect on the cross-linking efficiency of a DNA cross-linking agent, although these effects vary from agent to agent.


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FLANKING SEQUENCE EFFECTS, DNA, Diepoxides, interstrand cross-linking