Synthesis and Characterization of Oligonucleotides Containing a Nitrogen Mustard Formamidopyrimidine Monoadduct of Deoxyguanosine

• Published in: Chemical research in toxicology Vol. 27; no. 9; pp. 1610 - 1618
• Main Authors: Christov, Plamen P, Son, Kyu-Jun, Rizzo, Carmelo J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15-09-2014
• Subjects: Base Sequence; Deoxyguanosine - chemistry; Deoxyribonuclease IV (Phage T4-Induced) - metabolism; DNA Adducts - chemistry; DNA Repair; DNA-Formamidopyrimidine Glycosylase - metabolism; Electrophoresis, Agar Gel; Escherichia coli - enzymology; Escherichia coli Proteins - metabolism; Kinetics; Mechlorethamine - chemistry; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Organophosphorus Compounds - chemical synthesis; Organophosphorus Compounds - chemistry; Pyrimidines - chemistry
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx5002354

N 5-Substituted formamidopyrimidine adducts have been observed from the reaction of dGuo or DNA with aziridine containing electrophiles, including nitrogen mustards. However, the role of substituted Fapy-dGuo adducts in the biological response to nitrogen mustards and related species has not been extensively explored. We have developed chemistry for the site-specific synthesis of oligonucleotides containing an N 5-nitrogen mustard Fapy-dGuo using the phosphoramidite approach. The lesion was found to be a good substrate for Escherichia coli endonuclease IV and formamidopyrimidine glycosylase.