Structural influence of C8-phenoxy-guanine in the NarI recognition DNA sequence.

Phenoxyl radicals can covalently attach to the C8 site of 2′-deoxyguanosine (dG) to generate oxygen-linked biaryl ether C8-dG adducts. To assess the structural impact of an O-linked C8-dG adduct in duplex DNA, C8-phenoxy-G (PhOG) and C8-4-fluorophenoxy-G (4FPhOG) were incorporated into the G3 position of the 12-mer NarI recognition sequence (5′-CTCGGCXCCATC, where X = G, PhOG, or 4FPhOG) using solid-phase DNA synthesis with O-linked C8-dG phosphoramidites. The modified strands were hybridized to six different complementary strands that include regular base pairing to C [NarI′(C)], mismatches with G, A, T [NarI′(N)], and an abasic site [NarI′(THF)], and a 10-mer sequence to model a −2 deletion duplex [NarI′(−2)]. All duplex structures were characterized using UV–vis thermal melting temperature analysis, and in each instance, the O-linked C8-phenoxy-G adducts were found to destabilize the duplex relative to the unmodified controls. The most stable duplex structures match the O-linked C8-dG adduct against C ...