Inhibitory effect of DNA structure on the efficiency of reaction of guanosine moieties with a nitrenium ion

✍ Scribed by Michael Novak; Sonya A. Kennedy

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 134 KB
• Volume: 11
• Category: Article
• ISSN: 0894-3230
• DOI: 10.1002/(sici)1099-1395(199801)11:1<71::aid-poc973>3.0.co;2-h

✦ Synopsis

The N-acetyl-N-(2-fluorenyl)nitrenium ion (2a) reacts very efficiently with monomeric 2'deoxyguanosine (d-G) to form a C-8 adduct, N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene (6), in an aqueous environment, with a selectivity ratio, k d-G /k s , of 13.1 Â 10 3 M À1 at 0°C and 4.8 Â 10 3 M À1 at 30°C. The reactivity of the self-complementary oligomer d-ATGCAT with 2a can be separated into components due to the single-stranded (SS) and double-stranded (DS) forms. Within the error limits of the measurements k SS /k d-G % 0.27 and k DS /k d-G % 0. Another measure of the reactivity of d-G moieties in the DNA double helix can be obtained from measurements with the circular super-coiled plasmid pUC19. This plasmid provides an upper limit for k pUC19 /k d-G of 0.02, where k pUC19 is the average trapping rate constant per d-G moiety in pUC19. The strong inhibition of the trapping reaction caused by the tertiary structure of the DNA double helix may be responsible for the change in product distribution of 2a-d-G adducts found from reaction with d-G, and denatured DNA (exclusive C-8 adduct, 6) and native DNA [5-20% N-2 adduct,3-(2'-deoxyguanosin-N 2 -yl)-2-acetylaminofluorene, 7].