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Tris(tetramethylphenanthroline)ruthenium(II): a chiral probe that cleaves A-DNA conformations

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
..lambda..-Tris(3,4,7,8-tetramethyl-1,10-phenanthroline)ruthenium(II) (..lambda..-Ru(TMP)/sub 3//sup 2 +/) 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. ..lambda..-Ru(TMP)/sub 3//sup 2 +/ cleaves preferentially /sup 3/H-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)/sub 3//sup 2 +/ shows the selective binding of ..lambda..-Ru(TMP)/sub 3//sup 2 +/ to conformationally distinct sites along the fragment. These sites correspond to 5- to 13-base-pair homopyrimidine stretches.
Research Organization:
Columbia Univ., New York, NY (USA)
OSTI ID:
6647712
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 85:5; ISSN PNASA
Country of Publication:
United States
Language:
English