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The design and applications of a chiral probe for A-form nucleic acids tris(3,4,7,8-tetramethyl-1,10-phenanthroline) ruthenium (II) complex

Thesis/Dissertation ·
OSTI ID:6940437

A chiral metal complex and its interactions with various forms of nucleic acids were characterized in order to probe a specific for the A-conformation. Tris(3,4,7,8-tetramethyl-1,10-phenanthroline) ruthenium(II), Ru(TMP){sub 3}{sup 2+}, was synthesized and used to investigate both the global secondary structure and the local variations in conformation of polynucleotides. 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- or Z-form DNAs. The binding is accompanied by an enantiomeric selectivity for the {Lambda}-isomer, which is favored in surface binding. 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 {Lambda}-form polymers upon irradiation with visible light. Comparative mapping of cleavage sites on a linear pBR322 fragments 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 bonding of {Lambda}-Ru(TMP){sub 3}{sup 2+} to conformationally distinct sites along the fragment. Ru(TMP){sub 3}{sup 2+} was applied to investigate the structures of the promoter regions of Xenopus 5S RNA gene and Simian Virus 40 DNA. Specific sites for Ru(TMP){sub 3}{sup 2+} were found in these two promoter sequences and conformational heterogeneity were thus proposed in these important control regions.

Research Organization:
Columbia Univ., New York, NY (USA)
OSTI ID:
6940437
Country of Publication:
United States
Language:
English