322411-68-7

Upstream product

• 40615-36-9 4,4'-dimethoxytrityl chloride 
• 201605-71-2 1-(2'-Deoxy-β-D-erythro-pentafuranosyl)-7-nitroindole 
• 6960-42-5 7-nitro-1H-indole 
• 4330-21-6 2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl chloride 
• 218167-11-4 1-(2'-Deoxy-3',5'-di-O-p-toluoyl-β-D-erythro-pentafuranosyl)-7-nitroindole 

Relevant academic research and scientific papers

Histone-catalyzed cleavage of nucleosomal DNA containing 2-deoxyribonolactone

Oxidized abasic sites such as 2-deoxyribonolactone (L) are produced in DNA by a variety of oxidizing agents, including potent cytotoxic antitumor natural products. 2-Deoxyribonolactone is labile under alkaline conditions, but its half-life in free DNA at pH 7.5 is approximately 1 week. Independent generation of L at defined positions within nucleosomes reveals that the histone proteins catalyze strand scission and increase the rate between 11- and ～43-fold. Mechanistic studies indicate that DNA-protein cross-links are not intermediates en route to strand scission and that C2 deprotonation is the rate-determining step. The use of mutant histone H4 proteins demonstrates that the lysine-rich tail that is often post-translationally modified in cells contributes to the cleavage of L but is not the sole source of the enhanced cleavage rates. Consideration of DNA repair in cells suggests that L formation in nucleosomal DNA as part of bistranded lesions by antitumor antibiotics results in de facto double strand breaks, the most deleterious form of DNA damage.

The 7-nitroindole nucleoside as a photochemical precursor of 2′-deoxyribonolactone: Access to DNA fragments containing this oxidative abasic lesion

On the basis of molecular modeling studies, the 7-nitroindole nucleoside 1 was selected as a suitable photochemical precursor for photochemical generation of the C1′ deoxyribosyl radical under irradiation, which led to 2′-deoxyribonolactone. The nitroindole nucleoside derivatives 1a and 1b were prepared and their conformation was determined by X-ray crystallography and NMR spectroscopy. The photoreaction of these nucleosides gave the corresponding deoxyribonolactone derivatives efficiently, with release of 7-nitrosoindole. This reaction was successfully applied to synthesis of oligonucleotides containing the deoxyribonolactone lesion.