Mechanisms of Formation of Novel Guanine-Guanine Cross-Links as Major End Products during One-Electron Oxidation of Guanine Derivatives

Author

Evan DunnFollow

Honors Program

Honors in Chemistry

Date of Award

5-2023

Thesis Professor(s)

Marina Roginskaya

Thesis Professor Department

Chemistry

Thesis Reader(s)

Abbas Shilabin

Abstract

Guanine (G), as the most oxidizable base in DNA, is the major focus of studies of oxidation damage to DNA. The present thesis reports the first detailed characterization of G dimerization products potentially resulting from recombination of neutral G• radicals. Previous research has discovered a novel type of products of G• dimerization, D1 and D2, formed from one-electron oxidation of G derivatives. However, the mechanism of this dimerization remains elusive. While there appears to be a tautomeric equilibrium between two forms of G•, G(N₁-H)• or G(N₂-H)•, it remains unclear which intermediate participates in the formation of D1 and D2. By methylation at the N1 position, it was demonstrated by using reverse-phase HPLC and ¹H-NMR analysis that hydrogens at the exocyclic N2 position are absolutely required for the D1 and D2 analogs to be produced, while hydrogen at the N1 position is not required. This provides evidence in favor of the hypothesis that G(N₂-H)• is the major contributor to the pathway resulting in D1 and D2.

Publisher

East Tennessee State University

Document Type

Honors Thesis - Open Access

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Recommended Citation

Dunn, Evan, "Mechanisms of Formation of Novel Guanine-Guanine Cross-Links as Major End Products during One-Electron Oxidation of Guanine Derivatives" (2023). Undergraduate Honors Theses. Paper 780. https://dc.etsu.edu/honors/780

Copyright

Copyright by the authors.