Induced circular dichroism characteristics as conformational probes for carcinogenic aminofluorene-DNA adducts

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We report novel induced circular dichroism (ICD) characteristics for probing the conformational heterogeneity induced by the arylamine carcinogen 2-aminofluorene, namely, B type (B), stacked (S), and wedged (W) conformers. CD experiments were conducted with five different aminofluorene-modified DNA duplexes (I-V). An intense positive ICD was observed for the W conformeric I in the 290-360 nm range (IC290-360nm). This was in contrast to the negative ICD290-360nm exhibited by the mostly B conformeric V (17% S/83% B). Duplex IV, which adopts an approximately equal mixture of S (53%) and B (47%), exhibited low ellipticities along the baseline. The magnitude of the positive ICD for I was significantly greater than that observed for II (70% S/30% B). While the ICD290-360nm of the W conformeric III showed no changes in intensity with increasing temperature from 10 to 35 °C, dramatic changes were observed for I across the same temperature range. Dynamic 19F NMR results revealed that I exists in an 85:15 mixture of W and S/B conformers. The dramatic intensity changes observed for I are consistent with the presence of a W/B heterogeneity because of its susceptibility to result in a large difference on the magnitude of the ICD290-360nm. In conclusion, the sign and magnitude of the ICD290-360nm are sensitive conformational markers for studying arylamine-induced conformational heterogeneity. The temperature-dependent ICD290-360nm data, coupled with 19F NMR spectroscopy, provide valuable information about conformational distribution and dynamics, which are important factors that affect mutational outcomes. © 2006 American Chemical Society.

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Chemical Research in Toxicology