Theoretical analysis of DNA intrastrand cross linking by formation of 8,5'-cyclodeoxyadenosine.
Formation of intramolecular cross links by addition of C(5') deoxyribose radicals to the C(8)-N(7) double bond of an attached adenine base was analyzed by ab initio quantum-chemical methods. Conformational preferences that influence the stereospecificity of the reaction were investigated. A good correlation was found between the ratio of experimental yields of R and S stereoisomers of 8,5'-cyclodeoxyadenosine and the relative energy of conformations of the C(5') radical that are precursors to these isomers. Molecular mechanics based on the AMBER force field was used to model the effect of 8,5'-cyclodeoxyadenosine on the conformation of the DNA dodecamer d(CGCGAATTCGCG)2 with the lesion at the A6 position. The R and S stereoisomers of the intrastrand cross link cause comparable levels of DNA distortion with the major conformational changes occurring in backbone torsional angles at the site of the lesion.
Miaskiewicz
K
K
Environmental Molecular Sciences Laboratory, Pacific Northwest Laboratory, Richland, WA 99352.
Miller
J H
JH
Fuciarelli
A F
AF
D001483:Base Sequence; D003432:Cross-Linking Reagents; D004247:DNA / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry*; D003855:Deoxyribose; D005609:Free Radicals; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics
D003432:Cross-Linking Reagents; D003839:Deoxyadenosines; D005609:Free Radicals; D009838:Oligodeoxyribonucleotides; C056752:8,5'-cyclo-2'-deoxyadenosine; D003855:Deoxyribose; D004247:DNA