Oligodeoxynucleotides covalently linked to intercalating agents: a new class of gene regulatory substances

Hélène, Claude; Montenay-Garestier, Thérèse; Saison, T.; Takasugi, Masashi; Toulmé, Jean Jacques; Asseline, Ulysse; Lancelot, G.; Maurizot, Jean‐Claude; Toulme, Francine; Thuong, Nguyen T.

doi:10.1016/s0300-9084(85)80167-x

Cited by 92 publications

(54 citation statements)

References 8 publications

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“…Several interesting observations can be made: (i) Attachment of the acridine derivative to a-(Tp)7T at either the 5' or the 3' end leads to a stabilization of the complexes, as previously observed with the p analogs (13)(14)(15).…”

Section: Binding Of A-(tp)7t To Oligo-and Polyadenylatesmentioning

confidence: 62%

“…The hypochromicities are smaller with the a-oligonucleotides, but the most striking difference comes from the absence of the strong new absorption band at long wavelengths which was induced upon binding of 8-(Tp)8m5Acr to poly(rA) and-to a lesser extentto r(Ap)7rA (13)(14)(15). Only in the case of a-Acrm5(pT)8 binding to d(pA)8 is there any evidence for an increased absorbance on the long-wavelength side (see Fig.…”

Section: Binding Of A-(tp)7t To Oligo-and Polyadenylatesmentioning

confidence: 98%

“…Covalent attachment of an acridine derivative to the 5' or 3' end of the a-oligothymidylate strongly stabilizes the complexes with the complementary sequence as already observed with the /3-oligomers. This is attributed to the additional binding energy provided by the intercalation of an acridine ring between the base pairs of the miniduplex structure formed by the oligonucleotide with its complementary target sequence (13)(14)(15). The most stable complex is obtained when the acridine is attached to the 5' end of the a-oligonucleotide.…”

Section: Stability Of A-oligothymidylates Towards Nucleasesmentioning

confidence: 99%

“…Miller and co-workers have shown that oligophosphonates can penetrate into cells in culture and remain stable with respect to nucleases (11,12). We have recently reported the synthesis of oligodeoxynucleotides covalently linked to intercalating agents (13)(14)(15). The oligonucleotide keeps its binding specificity towards its complementary sequence, while the intercalating agent provides an additional binding energy that stabilizes the complex.…”

mentioning

confidence: 99%

“…The oligonucleotide keeps its binding specificity towards its complementary sequence, while the intercalating agent provides an additional binding energy that stabilizes the complex. The covalent linkage at the 5' end or 3' end of the oligonucleotide protects it against exonucleases (but not against endonucleases) and facilitates the uptake of the oligonucleotide by cells in culture (15). These modified oligonucleotides can block mRNA translation in a specific way (16).…”

mentioning

confidence: 99%

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Oligo(alpha-deoxynucleotide)s covalently linked to intercalating agents: differential binding to ribo- and deoxyribopolynucleotides and stability towards nuclease digestion.

Thuong¹,

Asseline²,

Roig³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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116

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An octathymidylate was synthesized with the a anomer of thymidine instead of the naturally occurring ,8 anomer. This oligonucleotide binds to complementary sequences containing j-nucleosides. Binding to ribose-containing oligomers and polymers is much stronger than binding to deoxyribose-containing analogs. A derivative of acridine (9-amino-6-chloro-2-methoxyacridine) was covalently attached either to the 5' phosphate or to the 3' phosphate of the ci-octathymidylate. A pentamethylene linker was used to bridge the phosphate group and the 9-amino group of the acridine derivative. In both cases the complexes with the complementary sequences were strongly stabilized due to the additional binding energy provided by intercalation of the acridine ring within the miniduplex structure formed by the oligonucleotide with its target sequence. The acridine-substituted a-oligothymidylates did not lose their discrimination between ribose and deoxyribose-containing complementary sequences. The a-oligothymidylates were much more resistant towards endonucleases than their I analogs, independently of whether they were linked to the acridine derivative. Acridine substitution provided additional protection against the corresponding exonucleases. a-Oligodeoxynucleotides covalently linked or not to intercalating agents represent families of molecules that open possibilities to block mRNA translation or viral RNA expression in vitro and in vivo.The regulation of gene expression in living organisms is achieved in most cases by specific proteins that recognize either a defined base (base-pair) sequence or a local conformation, which may result from the folding of the polynucleotide backbone and involve regions that are far apart in the primary sequence (1). It has been recently demonstrated that small RNAs, at least in bacteria, could also be involved in the regulation of gene expression by blocking translation through hybridization with mRNAs (2). Anti-sense RNAs have been used to specifically arrest protein synthesis in prokaryotic as well as eukaryotic systems (2-6). Synthetic oligodeoxynucleotides complementary to mRNAs can play the same role (7-10). The use of oligonucleotides to block mRNA translation in vivo is limited, however, by their sensitivity to nucleases and their poor penetration into cells in culture. To overcome these problems different modifications of oligonucleotides have been described. Miller and co-workers have shown that oligophosphonates can penetrate into cells in culture and remain stable with respect to nucleases (11,12). We have recently reported the synthesis of oligodeoxynucleotides covalently linked to intercalating agents (13-15). The oligonucleotide keeps its binding specificity towards its complementary sequence, while the intercalating agent provides an additional binding energy that stabilizes the complex. The covalent linkage at the 5' end or 3' end of the oligonucleotide protects it against exonucleases (but not against endonucleases) and facilitates the uptake of the oligonucleotide by cel...

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Section: Binding Of A-(tp)7t To Oligo-and Polyadenylatesmentioning

confidence: 62%

Section: Binding Of A-(tp)7t To Oligo-and Polyadenylatesmentioning

confidence: 98%

Section: Stability Of A-oligothymidylates Towards Nucleasesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Oligo(alpha-deoxynucleotide)s covalently linked to intercalating agents: differential binding to ribo- and deoxyribopolynucleotides and stability towards nuclease digestion.

Thuong¹,

Asseline²,

Roig³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

116

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Nucleic Acids

Burtscher

Berner

Seibl

et al. 2000

Ullmann's Encyclopedia of Industrial Chemistry

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The article contains sections titled: 1. Introduction 2. Structure 2.1. Structure of DNA 2.2. Structure of RNA 3. Properties 3.1. Physical and Chemical Properties 3.2. Interaction with Proteins 4. Biosynthesis and Biological Function 4.1. DNA Replication 4.2. Gene Expression 4.2.1. Transcription 4.2.2. Translation 4.3. Modification and Degradation 4.4. Recombination 4.5. DNA Repair 4.6. Nucleic Acids as Enzymes 5. Isolation, Purification, and Transfer 6. Analysis of Nucleic Acids 7. Chemical Synthesis 7.1. Synthesis Strategy 7.2. Protecting Groups 7.3. Functionalization of the Support 7.4. Methods of Synthesis 7.5. Cleavage of Protecting Groups and Purification of Oligonucleotides 7.6. Synthesis of Modified Oligonucleotides 8. Uses 8.1. Hybridization Techniques for Nucleic Acid Detection 8.2. Labeling and Detection Systems 8.3. Amplification Systems 8.4. Applications of Probe Technology 9. Nucleosides and Nucleotides 9.1. Nucleosides 9.2. Nucleotides 9.3. Therapeutically Important Nucleoside and Nucleotide Derivatives

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