INHIBITORY EFFECT OF DNA-STRUCTURE ON THE EFFICIENCY OF REACTION OF GUANOSINE MOIETIES WITH A NITRENIUM ION

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'-de oxyguanosin-8-yl)-2-acetylaminofluorene (6), in an aqueous environment , with a selectivity ratio, k(d-G)/k(s), of 13.1 x 10(3) M-1 at 0 degr ees C and 4.8 x 10(3) M-1 at 30 degrees C. The reactivity of the self- complementary oligomer d-ATGCAT with 2a can be separated into componen ts due to the single-stranded (SS) and double-stranded (DS) forms. Wit hin the error limits of the measurements k(SS)/k(d-G) approximate to 0 .27 and k(DS)/k(d-G) approximate to 0. Another measure of the reactivi ty of d-G moieties in the DNA double helix can be obtained from measur ements with the circular super-coiled plasmid pUC19. This plasmid prov ides 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 in hibition of the trapping reaction caused by the tertiary structure of the DNA double helix may be responsible for the change in product dist ribution 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 3-(2'-deoxygu anosin-N-2-yl)-2-acetylaminofluorene, 7]. (C) 1998 John Wiley & Sons, Ltd.