Induced circular dichroism characteristics as conformational probes for carcinogenic aminofluorene-DNA adducts.
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 (ICD(290)(-)(360nm)). This was in contrast to the negative ICD(290)(-)(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 ICD(290)(-)(360nm) of the W conformeric III showed no changes in intensity with increasing temperature from 10 to 35 degrees C, dramatic changes were observed for I across the same temperature range. Dynamic (19)F 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 ICD(290)(-)(360nm). In conclusion, the sign and magnitude of the ICD(290)(-)(360)(nm) are sensitive conformational markers for studying arylamine-induced conformational heterogeneity. The temperature-dependent ICD(290)(-)(360nm) data, coupled with (19)F NMR spectroscopy, provide valuable information about conformational distribution and dynamics, which are important factors that affect mutational outcomes.
Liang
Fengting
F
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 41 Lower College Road, Kingston, Rhode Island 02881, USA.
Meneni
Srinivasarao
S
Cho
Bongsup P
BP
D001665:Binding Sites; D002273:Carcinogens / Q000737:chemistry*; D002942:Circular Dichroism; D018736:DNA Adducts / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation
C052668:2-aminofluorene-DNA complex; D002273:Carcinogens; D018736:DNA Adducts; D005449:Fluorenes