"Probing the Mechanism of DNA Protein Crosslink Formation by Aziridinom" by Michael Blair

Publication Date

8-2023

Date of Final Oral Examination (Defense)

June 2023

Type of Culminating Activity

Thesis

Degree Title

Master of Science in Chemistry

Department Filter

Chemistry

Department

Chemistry and Biochemistry

Supervisory Committee Chair

Don L. Warner, Ph.D.

Supervisory Committee Member

Ken Cornell, Ph.D.

Supervisory Committee Member

Michael P. Callahan, Ph.D.

Abstract

Aziridinomitosenes are synthetic chemotherapeutic agents that are analogs of Mitomycin C, as well as other mitomycins. They are known for their ability to form DNA interstrand cross-links (ICLs), and more recently have been observed to form DNA-protein cross-links (DPCs). In this work, three synthetic aziridinomitsenes were prepared and studied to better understand the role of the C6 and C7 positions in the formation of DNA-protein cross-links. In addition, two separate methods, the advanced recovery of K-SDS precipitates and the K-SDS assays were utilized and compared to assess the advancements in the analysis of DPC formation. H AZM, C6 AZM, Dimethyl AZM, and Mitomycin C were compared to formaldehyde, a known DNA-protein cross-linking agent in these techniques. Results from the ARK assay displayed a 4-fold increase in average response in nearly every treatment group when compared to the previously developed K-SDS method. Additionally, the ARK assay provided tighter standard deviations indicating more reliable data. Analysis of ARK data displayed that the C6 AZM was capable of forming a greater percentage of DNA-protein cross-links compared to the H AZM and Dimethyl AZM. These results indicated that the C6 and C7 positions of aziridinomitosenes play an important role in DNA-protein cross-link formation.

DOI

https://doi.org/10.18122/td.2152.boisestate

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