Tris(tetramethylphenanthroline)ruthenium(II): A chiral probe that cleaves A-DNA conformations
A-Tris(3,4,7,8-tetramethyl-1,10-phenanthroline) ruthenium(II) [A-Ru(TMP)2/3+] was found to be a distinctive molecular tool to examine the local variations in conformation along the strand. The metal complex binds cooperatively to A-form helices of various base sequences under conditions where little or no binding was found to analogous B-form DNAs. Photoactivated DNA cleavage may be coupled to this conformation-specific binding by taking advantage of the photophysical properties of ruthenium(II) complexes. A(TMP)2/3+ cleaves preferentially 3H-labeled A-form polynucleotides upon irradiation with visible light. The photoinduced DNA strand scission is likely to be mediated by singlet oxygen, which leads to a preferential cleavage of guanine residues. Comparative mapping of cleavage sites on a linear pBR322 fragment for tris(phenanthroline)ruthenium(II), which binds to B-DNA and cleaves also by sensitization of singlet oxygen, and for Ru(TMP)2/3+ shows the selective binding of ARu(TMP)2/3+ to conformationally distinct sites along the fragment. These sites correspond to 5- to 13-base-pair homopyrimidine stretches.
Copyright © 1988 by the National Academy of Sciences. Communicated by Nicholas J. Turro, October 9, 1987. We thank N. J. Turro, C. V. Kumar, and D. Patel for helpful discussions. This work was supported by grants from the National Institutes of Health (GM33309) and the National Science Foundation (CHE85-17354, Alan T. Waterman Award to J.K.B.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Published - MEIpnas88.pdf