Recognition of DNA Base Mismatches by a Rhodium Intercalator

Jackson, Brian A.; Barton, Jacqueline K.

doi:10.1021/ja972489a

Cited by 123 publications

(149 citation statements)

References 36 publications

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“…This observation corroborates the direct correlation between the binding affinity of Δ-Rh(bpy-d 8 ) 2 chrysi 3+ for mismatches and the extent to which these mismatches destabilize DNA. [1][2][3] The C 2 symmetry of the palindromic oligonucleotide is broken upon insertion of the rhodium complex resulting in two distinct strands. Consequently, the two ejected bases are no longer equivalent: one of the two mismatched cytosines is significantly more flexible than the other.…”

Section: Resultsmentioning

confidence: 99%

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Insertion of a Bulky Rhodium Complex into a DNA Cytosine−Cytosine Mismatch: An NMR Solution Study

2007

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The bulky octahedral complex, Rh(bpy) 2 chrysi 3+ (chrysi = 5, 6-chrysenequinone diimine), binds single base mismatches in a DNA duplex with micromolar binding affinities and high selectivity. Here we present an NMR solution study to characterize the binding mode of this bulky metal complex with its target CC mismatch in the oligonucleotide duplex (5′-CGGACTCCG-3′) 2 . Both NOESY and COSY studies indicate that Rh(bpy) 2 chrysi 3+ inserts deeply in the DNA at the mismatch site via the minor groove and with ejection of both destabilized cytosines into the opposite major groove. The insertion only minimally distorts the conformation of the oligonucleotide local to the binding site. Both flanking, well-matched base pairs remain tightly hydrogen-bonded to each other, and 2D DQF-COSY experiments indicate that all sugars maintain their original C2′ endo conformation. Remarkably, 31 P NMR reveals that opening of the phosphate angles from a B I to a B II conformation is sufficient for insertion of the bulky metal complex. These results corroborate those obtained crystallographically and, importantly, provide structural evidence for this specific insertion mode in solution.

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Section: Resultsmentioning

confidence: 99%

“…[1][2][3] Rh(bpy) 2 chrysi 3+ (chrysi = 5,6-chrysenequinone diimine, Figure 1), is a sterically bulky DNA intercalator that binds specifically in the destabilized regions near DNA base mismatches and, upon photoactivation, cleaves the DNA backbone. The complex is both a general and remarkably specific mismatch recognition agent.…”

Section: Introductionmentioning

confidence: 99%

Insertion of a Bulky Rhodium Complex into a DNA Cytosine−Cytosine Mismatch: An NMR Solution Study

2007

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“…In recent years, we have applied our understanding of molecular recognition elements to the development of complexes that selectively bind mispaired sites in DNA [3][4][5] . DNA mismatches occur in the cell as a result of polymerase errors or DNA damage 6,7 .…”

Section: Introductionmentioning

confidence: 99%

“…2) 3,13 . The preparation of the simplest complexes in each family, Rh(bpy) 2 (chrysi) 3+ and Rh(bpy) 2 (phzi) 3+ , is described here.…”

Section: Introductionmentioning

confidence: 99%

“…Site selectivity in solution can be readily discerned through DNA photocleavage experiments. In addition to binding mismatches tightly and selectively, the complexes promote direct strand scission adjacent to the mismatch site with photoactivation 3,13 . The selectivity of the complexes is a tremendous asset; Rh(bpy) 2 (chrysi) 3+ , for example, is capable of binding and cleaving a single CC mismatch in a 2,725 bp plasmid 4 .…”

Section: Introductionmentioning

confidence: 99%

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DNA base mismatch detection with bulky rhodium intercalators: synthesis and applications

Zeglis

Barton

2007

Nat Protoc

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This protocol describes the syntheses and applications of two metallointercalators, Rh(bpy) 2 (chrysi) 3+ and Rh(bpy) 2 (phzi) 3+ , that target single base mismatches in DNA. The complexes bind mismatched DNA sites specifically and, upon photoactivation, promote strand scission neighboring the mismatch. Owing to their high specificity and sequence context independence, targeting mismatches with these complexes offers an attractive alternative to current mismatch-and SNP-detection methodologies. This protocol also describes the synthesis of these complexes and their use in marking mismatched sites. Irradiation of 32 P-labeled duplex DNA with either intercalator followed by denaturing PAGE allows the detection of mismatches in oligonucleotides. The protocol also outlines a method for efficient detection of single nucleotide polymorphisms (SNPs) in larger genes or plasmids. Pooled genes are denatured and re-annealed to form heteroduplexes; they are then incubated with either complex, irradiated and analyzed using capillary electrophoresis to probe for mismatches (SNP sites). The synthesis of the metallointercalators requires approximately 5-7 d. The mismatch-and SNP-detection experiments each require approximately 3 d.

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Probing Nucleic Acid Structure with Shape‐Selective Rhodium and Ruthenium Complexes

Barton

2000

CP Nucleic Acid Chemistry

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In this unit, transition metal complexes are used as photochemical probes for the structure of RNA and DNA. The transition metal ion provides a rigid substitutionally inert framework and an octahedral geometry for ligand coordination. The complexes can be constructed to define shapes, symmetries, and functionalities that complement those of the nucleic acid target. Complex formation is easily detected by light-induced nucleic acid cleavage. The modular construction of the complexes makes it possible to generate probes to examine a wide variety of structural characteristics of nucleic acids.

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Recognition of DNA Base Mismatches by a Rhodium Intercalator

Cited by 123 publications

References 36 publications

Insertion of a Bulky Rhodium Complex into a DNA Cytosine−Cytosine Mismatch: An NMR Solution Study

Insertion of a Bulky Rhodium Complex into a DNA Cytosine−Cytosine Mismatch: An NMR Solution Study

DNA base mismatch detection with bulky rhodium intercalators: synthesis and applications

Probing Nucleic Acid Structure with Shape‐Selective Rhodium and Ruthenium Complexes

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