Studies on the Adduct Heterogeneity of Benzo(a)pyrene 7,8-Dihydrodiol 9,10-Epoxide Stereoisomers Covalently Bound to Deoxyribooligonucleotides by Induced Circular Dichroism and Light Absorption Spectroscopy
Artikel i vetenskaplig tidskrift, 1999
The binding conformations of single anti- and syn-BPDE-N-2-dG adducts in oligonucleotides of varying base composition have been studied by induced circular dichroism (ICD) and light absorption spectroscopy. The sign of the ICD in single-stranded oligonucleotide adducts correlates with the absolute configuration of the cyclohexyl moiety of the BPDE. Adducts in oligonucleotide duplexes with UV lambda(max) <350 nm exhibiting a significant duplex-induced positive ICD should have a minor groove location as the predominant conformation. Those with UV lambda(max) >350 nm exhibiting either positive or negative contributions to the ICD should have intercalated binding as the predominant conformation. The magnitude of the ICD is dependent on the sequence context of the adducted strand and the particular BPDE-adduct isomer under study. In some cases, the results suggest structural heterogeneity. For instance, the (+)- and the (-)-trans-anti-BPDE-N-2-dG adducts in duplexes where a dT flanks the lesion site exhibit weak positive ICD or negative ICD. These results reflect a bimodal conformational adduct distribution with contributions from both externally and internally located adducts. A key observation for the (+)-cis-syn-BPDE-N-2-dG complexes in 5'-d(TGC) and 5'-d(CGC) sequence contexts is that the near-UV absorption spectra showed distinct bands corresponding to minor groove binding (lambda(max) congruent to 346 nm) as well as intercalative binding (lambda(max) congruent to 354 nm). Evidence for an equilibrium between the different modes of localization is provided by the results from the temperature dependence of the near-UV absorption and ICD characteristics of(+)-cis-synBPDE-N-2-dG complexes in 5'-d(TGC) and 5'-d(CGC) sequence contexts, respectively.