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Published April 1994 | metadata_only
Journal Article

Correlations of Crystal Structures of DNA Oligonucleotides with Enantioselective Recognition by Rh(phen)_2phi^(3+): Probes of DNA Propeller Twisting in Solution


Rh(phen)_2phi^(3+) (phen = 1,10-phenanthroline; phi= 9,10-phenanthrenequinonediimine) avidly binds to DNA via intercalation from the major groove and upon photoactivation produces strand scission with single base 5' asymmetry. Enantiomers of Rh(phen)_2phi^(3+), which lack hydrogen-bonding substituents in ancillary positions, distinguish a DNA site through shape-selection; site recognition depends upon the local variations in structure at a binding site. Here, we examine the application of Δ-Rh(phen)_2phi^(3+) as a sequence-dependent structural probe and, in particular, as a probe of DNA propeller twisting in solution, by comparing directly cleavage results using Δ- and Λ-Rh(phen)_2phi^(3+) on crystallographically characterized oligonucleotides with several sequence-dependent crystallographic parameters. The three oligonucleotides examined in this study are the Dickerson-Drew dodecamer, 5'-CGCGAA TTCGCG-3', the Nar I dodecamer, 5'-ACCGGCGCCACA-3', and the CG decamer, 5'-CCAACGTTGG-3', all of which have been crystallized in the B-form. Enantioselective cleavage and reaction favored by the Δ-isomer is found to be governed locally by the opening of the site in the major groove. A correlation is demonstrated between cleavage by Δ-Rh(phen)_2phi^(3+) and the opening in the major groove that results from the change in propeller twist (differential propeller twist) at a base step. When the major groove is closed as a result of a change in propeller twist, there is little cleavage evident by either enantiomer; at sites which are indicated crystallographically to be open in the major groove, a direct correlation is observed between enantioselective cleavage and the degree of opening. A trend of higher enantioselectivity at sites possessing higher twist angles is also observed. The roll angle of a site in isolation, the rise per base step, and the groove width show no correlation with cleavage. The distribution of reaction products at a site, as a result of partitioning along oxygen-dependent or oxygen-independent pathways, also provides a sensitive measure of the shapecomplementarity between metal complex and binding site. These results provide evidence for site-recognition by the metal complex which correlates directly with DNA propeller twisting in oligonucleotide crystals. Importantly, these results indicate that Rh(phen)_2phi^(3+) may be uniquely applied as a chemical probe for sequence-dependent changes in the propeller twisting of DNA.

Additional Information

© 1994 American Chemical Society. Received November 4, 1993; Revised Manuscript Received January 27, 1994. Publication Date: April 1994. We are grateful to the National Institutes of Health (GM33309 and an NRSA predoctoral traineeship to D.C.) for their financial support. We thank S. David for providing enantiomerically pure rhodium complexes.

Additional details

August 20, 2023
August 20, 2023