Date of Award
2003
Document Type
Honors Thesis (Open Access)
Department
Colby College. Chemistry Dept.
Advisor(s)
Julie T. Millard
Second Advisor
Jeffrey A. Katz
Abstract
Diepoxybutane, diepoxyoctane, and mechlorethamine are cytotoxic DNA crosslinking agents that vary in their carcinogenic versus chemotherapeutic potentials. Interstrand cross-linking occurs between the N7 positions of deoxyguanosine residues on opposite strands of the DNA duplex. Each synthetic DNA oligomer used in this study contained four 5'-N\GN2CN3 sites (within a 32 base sequence) and we have systematically varied the bases in the N1 and N2 positions to determine the resulting cross-linking efficiencies of each cytotoxic agent. Each duplex was 5' -end labeled and incubated with cross-linking agent. Interstrand cross-links were purified through denaturing polyacrylamide gel electrophoresis and then subjected to piperidine cleavage. The amount of cleavage at each deoxyguanosine residue was determined by sequencing gel analysis and represents the cross-linking efficiency at that site. We have determined that cross-linking efficiency varies with the identity of Nl and N2.
Keywords
Carcinogens Cancer, Genetic aspects, DNA-ligand interactions, Diepoxybutane, diepoxyoctane, mechlorethamine
Recommended Citation
Sawyer, Gregory A., "Flanking Sequences Modulate Diepoxide Cross-linking Efficiencies at the 5'-GNC sSte" (2003). Honors Theses. Paper 233.https://digitalcommons.colby.edu/honorstheses/233
Copyright
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