Published online 30 January 2006
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Sequence effects of aminofluorene-modified DNA duplexes: thermodynamic and circular dichroism properties
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island Kingston, RI 02881, USA 1Department of Chemistry, Loyola University Chicago, IL 60626, USA
*To whom correspondence should be addressed at Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 41 Lower College Road, Kingston, RI 02881, USA. Tel: +1 401 874 5024; Fax: +1 401 874 5766; Email: bcho{at}uri.edu
Received December 7, 2005. Revised January 14, 2005. Accepted January 14, 2005.
Circular dichroism (CD) and UV-melting experiments were conducted with 16 oligodeoxynucleotides modified by the carcinogen 2-aminofluorene, whose sequence around the lesion was varied systematically [d(CTTCTNG[AF]NCCTC), N = G, A, C, T], to gain insight into the factors that determine the equilibrium between base-displaced stacked (S) and external B-type (B) duplex conformers. Differing stabilities among the duplexes can be attributed to different populations of S and B conformers. The AF modification always resulted in sequence-dependent thermal (Tm) and thermodynamic (
G°) destabilization. The population of B-type conformers derived from eight selected duplexes (i.e. -AG*N- and -CG*N-) was inversely proportional to the
G° and Tm values, which highlights the importance of carcinogen/base stacking in duplex stabilization even in the face of disrupted WatsonCrick base pairing in S-conformation. CD studies showed that the extent of the adduct-induced negative ellipticities in the 290350 nm range is correlated linearly with
G° and Tm, but inversely with the population of B-type conformations. Taken together, these results revealed a unique interplay between the extent of carcinogenic interaction with neighboring base pairs and the thermodynamic properties of the AF-modified duplexes. The sequence-dependent S/B heterogeneities have important implications in understanding how arylamineDNA adducts are recognized in nucleotide excision repair.
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