TY - JOUR
T1 - Linear dichroism properties and orientations of different ultraviolet transition moments of benzo[a]pyrene derivatives bound noncovalently and cova
AU - Roche, Camille J.
AU - Geacintov, Nicholas E.
AU - Ibanez, Victor
AU - Harvey, Ronald G.
N1 - Funding Information:
This work was supported by Grant CA 20851, the U.S. Public Health Service, Department of Health and Human Resources, awarded by the National Cancer Institute, and in part by the Office of Environmental Health Research, De- partment of Energy (Grants DEFGO2-86ER60405 and DEFGO2-288ER60674). At the University of Chicago, the work was supported by Grant ES 04732, the U.S. Public Health Service, Department of Health and Human Resources, awarded by the National Institute of Environmental Health Sciences, and by Grant BC 132, awarded by the American Cancer Society. The assistanceo f Dr. Y. Mnyukh with the linear dichroism experiments is gratefully acknowledged. Based in part on the Ph.D. dissertation of C.J.R., New York University, February 1988.
PY - 1989/7
Y1 - 1989/7
N2 - Linear dichroism and absorption methods are used to study the orientations of transition moments of absorption bands of polycyclic aromatic epoxide derivatives which overlap with those of the DNA band in the 240-300 nm region. Both the short and long axes of the pyrene residues of 1-oxiranylpyrene (1-OP) and the (+) and (-) enantiomers of trans-7, 8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) noncovalently bound to double-stranded native DNA are oriented approximately perpendicular to the axis of the DNA helix, consistent with intercalative modes of binding. The covalent binding of these three epoxide derivatives to DNA is accompanied by reorientations of both the short and long axes of the pyrene residues. Covalent adducts derived from the highly mutagenic (+)-anti-BPDE are characterized by tilts of the short axis within 35 ° or less, and of the long axis by more than 60-80 °, with respect to the planes of the DNA bases. In the adducts derived from the binding of the less mutagenic (-)-anti-BPDE and 1-OP epoxide derivatives to DNA, the long axes of the pyrenyl rings are predominantly oriented within 25 ° of the planes of the DNA bases; however, in the case of the (-) enantiomer of BPDE, there is significant heterogeneity of conformations. In the case of the 1-OP covalent DNA adducts, the short axis of the pyrene ring system is tilted away from the planes of the DNA bases, and the pyrene ring system is not intercalated between DNA base-pairs as in the noncovalent complexes. The stereochemical properties of the saturated 7,8,9,10-ring in BPDE, or the lack of the 7 and 8 carbon atoms in 1-OP, do not seem to affect noncovalent intercalative complex formation which, most likely, is influenced mainly by the flat pyrenyl residues. These structural features, however, strongly influence the conformations of the covalent adducts, which in turn may be responsible for the differences in the mutagenic activities of these molecules.
AB - Linear dichroism and absorption methods are used to study the orientations of transition moments of absorption bands of polycyclic aromatic epoxide derivatives which overlap with those of the DNA band in the 240-300 nm region. Both the short and long axes of the pyrene residues of 1-oxiranylpyrene (1-OP) and the (+) and (-) enantiomers of trans-7, 8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) noncovalently bound to double-stranded native DNA are oriented approximately perpendicular to the axis of the DNA helix, consistent with intercalative modes of binding. The covalent binding of these three epoxide derivatives to DNA is accompanied by reorientations of both the short and long axes of the pyrene residues. Covalent adducts derived from the highly mutagenic (+)-anti-BPDE are characterized by tilts of the short axis within 35 ° or less, and of the long axis by more than 60-80 °, with respect to the planes of the DNA bases. In the adducts derived from the binding of the less mutagenic (-)-anti-BPDE and 1-OP epoxide derivatives to DNA, the long axes of the pyrenyl rings are predominantly oriented within 25 ° of the planes of the DNA bases; however, in the case of the (-) enantiomer of BPDE, there is significant heterogeneity of conformations. In the case of the 1-OP covalent DNA adducts, the short axis of the pyrene ring system is tilted away from the planes of the DNA bases, and the pyrene ring system is not intercalated between DNA base-pairs as in the noncovalent complexes. The stereochemical properties of the saturated 7,8,9,10-ring in BPDE, or the lack of the 7 and 8 carbon atoms in 1-OP, do not seem to affect noncovalent intercalative complex formation which, most likely, is influenced mainly by the flat pyrenyl residues. These structural features, however, strongly influence the conformations of the covalent adducts, which in turn may be responsible for the differences in the mutagenic activities of these molecules.
KW - Benzo[a]pyrene derivative
KW - DNA adduct
KW - DNA binding
KW - Diol epoxide
KW - Linear dichroism
KW - Ultraviolet transition moment
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U2 - 10.1016/0301-4622(89)80029-8
DO - 10.1016/0301-4622(89)80029-8
M3 - Article
C2 - 2508781
AN - SCOPUS:0024342577
SN - 0301-4622
VL - 33
SP - 277
EP - 288
JO - Biophysical Chemistry
JF - Biophysical Chemistry
IS - 3
ER -