Nonenzymatic sequence-specific cleavage of single-stranded DNA.

Abstract

Ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid have been attached covalently to the 5' terminus of the deoxynucleotide sequence C-A-C-A-A-T-T-C-C-A-C-A-C-A-A-C (16-mer) via an ethylenediamine linker. In the presence of Fe2+ and dithiothreitol, these reagents bring about the hybridization-dependent cleavage of the sequence T-C-G-T-A-T-G-T-T-G-T-G-T-G-G-A-A-T-T-G-T-G-A-G-C-G-G-A-T-A-A-C-A-A-T-T- T (37-mer), a sequence that contains an internal subsequence complementary to the 16-mer. The principal cleavage sites on the 37-mer are about four residues on each side of the terminal phosphate group of the 16-mer.

Sequence-Specific Cleavage of Double Helical DNA by Triple Helix Formation

“…Oligonucleotides equipped with a DNA cleaving moiety have been described which produce sequence-specific cleavage of single-stranded DNA (25-28). An example of this is oligonucleotide-EDTAFe hybridization probes (DNA-EDTA) which cleave the complementary single strand sequence (26,27). A homopyrimidine oligonucleotide equipped with a DNA cleaving moiety should recognize the corresponding complementary sequence of double helical homopurinehomopyrimidine DNA and yield a strand break at the target sequence (Fig.…”

Oxidative DNA Cleavage with Clip‐Phenanthroline Triplex‐Forming Oligonucleotide Hybrids

“…Artificial metallonucleases (AMNs) have also attracted much attention as tools to introduce dsDNA breaks, but sequence specificity remains a major challenge. Diverse metal complexes, including iron(II), [11][12][13][14][15][16] cerium(IV), [17] zirconium(IV), [18] rhenium(I), [19] rhodium(II) [20] and manganese, [21] were linked to modified oligonucleotides (ONs) or to minor-groove binders and were shown to cleave DNA with certain selectivity, which was mostly far below any useful level. Copper(I) complexes with diverse ligands are known to be excellent DNA cleaving agents.…”

The 1988 Walter Hubert lecture: Artificial control of gene expression by oligodeoxynucleotides covalently linked to intercalating agents

“…However, oligomethylphosphonates (unpublished results) and oligo-(ae)-deoxynucleotides (Gagnor et al, 1987) form hybrids with RNAs which are not cleaved by RNase H. These modified oligonucleotides are resistant to DNases and therefore their lifetime in living cells is considerably increased (Cazenave et al, 1987b (Chu & Orgel, 1985;Dreyer & Dervan, 1985;Boidot-Forget et al, 1986; phenanthroline-Cu (Chen & Sigman, 1986;Frangois et al, 1988a;Sun et al, 1988) and porphyrin-Fe (Le Doan et al, 1986Doan et al, , 1987a An intercalating agent such as proflavine can be used as a photosensitiser (Praseuth et al, 1988b). All the photoactive groups described until now lead to photocrosslinking of the oligonucleotide to its target sequence.…”