Circular dichroism of poly(dG-dC) modified by the carcinogens N-methyl-4-aminoazobenzene or 4-aminobipbenyl

Abstract

Poly(dG-dC) was modified to different extents by the carcinogens 4-aminobiphenyl (ABP) or N-methyl-4-aminoazobenzene (MAB). HPLC analysis of the enzymatically hydrolyzed modified polymers indicates that more than 90% of the ABP and 81% of the MAB modification occurs at the C8 position of guanine. The conformational changes of the unmodified and modified polymers were studied as a function of ethanol and magnesium ion concentrations by the use of circular dichroism (CD). The modified polymers show a CD inversion pattern similar to that of the salt-induced B to Z transition of poly(dG-dC). Both of the modified polymers require less salt or ethanol than the unmodified polymer for the inversion of the spectra. The amount of ethanol or magnesium needed to induce the inverted CD spectrum is inversely proportional to the percentage of bound ABP or MAB. These data indicate that ABP and MAB can enhance conversion from B to Z conformation in alternating purine-pyrimidine sequences.

mutation spectra of Glu‐P‐1 in Salmonella: Induction of hotspot frameshifts and site‐specific base substitutions

“…Such sequences can form Z-DNA, which is unstable and may result in a high frequency of spontaneous 2-base deletions [Freund et al, 19891. Although the conformation of Glu-P-l-adducted guanine has not, to our knowledge, been examined, both 2-AAF and 4-AB adducts of guanine have been shown to adopt the syn conformation, which may promote the B-to Z-DNA transition [Broyde et al, 1985;Shapiro et al, 1986;Abuaf et al, 1987;Burnouf et al, 19891. Consequently, the hotspot mutation may also result from the structural features of Z-DNA and/or the action of certain Z-DNA-binding proteins [e.g., Fishel et al, 19881 on such structures, especially on C(8) adducts on guanine in Z-DNA.…”

The conformational effect of para-substituted C8-arylguanine adducts on the B/Z-DNA equilibrium

“…Remarkably, C8-bromination [19] or methylation [20,21] eliminates the need for high salt concentrations. Other C8 substituents have been studied with respect to the B/Z DNA equilibrium, including aminofluorene [22], 4-aminobiphenyl [23], and phenyl [24]. Invariably, all cases of C8-purine substitution of Z-prone sequences have been found to shift the equilibrium toward the Z DNA form, though to different degrees.…”

Advancements in Z-DNA: Development of Inducers and Stabilizers for B to Z Transition

“…Based on the molecular model, the 8-phenyl group located in the major groove inside of the helix can induce a steric effect, destabilizing B-DNA and stabilizing the resulting Z-DNA [75][76][77]. Over the years, various C8-modifications have been developed to provide B-to Z-DNA transitions, including amino fluorene, amino biphenyl and a series of C8-para-substituents containing phenylguanine (Fig.…”