Photolabile N-hydroxypyrid-2(1H)-one derivatives of guanine nucleosides: a new method for independent guanine radical generation.
One-electron oxidized guanine is an important reactive intermediate in the formation of oxidatively generated damage in DNA and a variety of methods have been utilized for the abstraction of a single electron from the guanine moiety. In this study, an alternative approach for the site specific, independent generation of the guanine radical, utilizing N-hydroxypyrid-2(1H)-one as a photolabile modifier of guanine, is proposed. Novel photolabile 6-[(1-oxido-2-pyridinyl)oxo]-6-deoxy- and 2',6-dideoxy-guanosine derivatives capable of generating the neutral guanine radical (G(-H)*) upon photolysis were synthesized and characterized. The generation of G(-H)* proceeds through homolysis of the N-O bond and was confirmed through continuous photolysis product analysis and trapping studies, as well as laser flash photolysis experiments.
Kaloudis
Panagiotis
P
Organic Chemistry Laboratory, Department of Chemistry, University of Athens, Panepistimiopolis, 15771 Athens, Greece.
Paris
Cecilia
C
Vrantza
Despoina
D
Encinas
Susana
S
Pérez-Ruiz
Raul
R
Miranda
Miguel A
MA
Gimisis
Thanasis
T
D005609:Free Radicals / Q000138:chemical synthesis / Q000737:chemistry; D006150:Guanine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010782:Photolysis; D011728:Pyridones / Q000737:chemistry*; D013237:Stereoisomerism
D005609:Free Radicals; D006150:Guanine Nucleotides; D011728:Pyridones