Oligo-alpha-thymidylates covalently linked to intercalating agents: circular dichroism studies of their interaction with complementary sequences.

The interaction between oligo-alpha-thymidylates covalently linked to an intercalating agent (an acridine derivative) and their complementary sequences containing beta-nucleosides (poly(rA), poly(dA), r(Ap)7rA, p(dA)8) has been studied using circular dichroism spectroscopy. Binding to poly(rA) and to poly(dA) of the modified oligonucleotides led to large changes in the induced circular dichroism signal of the acridine ring. These changes depend on whether the dye is linked to the 3'- or to the 5'-end of the oligonucleotide. Interaction with poly(rA) as well as interaction with an octadeoxyriboadenylate led to the formation of a 1A:1T complex. With poly(dA), in addition to the 1A:1T complex, a 1A:2T complex was observed when the acridine derivative was linked to the 3'-end of the octa-alpha-thymidylate. The double-stranded structures formed with poly(rA) and poly(dA) were characterized by different environments of the acridine dye. Binding to poly(rA) gave much stronger complexes than binding to poly(dA). With poly(rA) the complex was more stable when the dye was bound at the 5'-end of the oligonucleotide. Comparison between the circular dichroism changes observed upon binding at the level of polymers [poly(rA) or poly(dA)] and those obtained at the level of oligomers [r(Ap)7rA or pd(A)8] gave information relative to the position of the acridine ring in the helix.

[1]  J. Toulmé,et al.  Inhibition of translation initiation by antisense oligonucleotides via an RNase-H independent mechanism. , 1991, Nucleic acids research.

[2]  F. Birg,et al.  Inhibition of simian virus 40 DNA replication in CV-1 cells by an oligodeoxynucleotide covalently linked to an intercalating agent. , 1990, Nucleic acids research.

[3]  C. Paoletti,et al.  Comparative activity of α- and β-anomeric oligonucleotides on rabbit β globin synthesis: Inhibitory effect of cap targeted α-oligonucleotides , 1989 .

[4]  C. Paoletti,et al.  α -DNA X: α and β tetrathymidilates covalently linked to oxazolopyridocarbazolium (OPC): comparative stabilization of oiigo β -[dT]:oligo β -[dA] and oligo α -[dT]:oligo β -[dA] duplexes by the intercalating agent , 1989 .

[5]  M. Durand,et al.  Thermodynamic parameters of the binding of an oligo-α-thymidylate to its complementary oligo-β-adenylate sequences , 1989 .

[6]  P. Emson,et al.  In situ hybridization histochemistry: localisation of vasopressin mRNA in rat brain using a biotinylated oligonucleotide probe. , 1988, Brain research.

[7]  M. Durand,et al.  Circular dichroism studies of an oligo-alpha-thymidylate and of its interactions with complementary sequences. , 1988, Nucleic acids research.

[8]  E. Wickstrom,et al.  alpha-Oligodeoxynucleotide stability in serum, subcellular extracts and culture media. , 1986, Journal of biochemical and biophysical methods.

[9]  N. Thuong,et al.  Rate of degradation of [α]- and [β]-oligodeoxynucleotides in Xenopus oocytes. Implications for anti-messenger strategies , 1987 .

[10]  N. Thuong,et al.  Selective inhibition of the cytopathic effect of type A influenza viruses by oligodeoxynucleotides covalently linked to an intercalating agent. , 1987, Nucleic acids research.

[11]  J. Lown,,et al.  α-DNA-V. Parallel annealing, handedness and conformation of the duplex of the unnatural α-hexadeoxyribonucleotide α-[d(CpApTpGpCpG)] with its β-complement β-[d(GpTpApCpGpC)] deduced from high field 1H-NMR , 1987 .

[12]  C. Paoletti,et al.  α-DNA IV: α-anomeric and β-anomeric tetrathymidylates covalently linked to intercalating oxazolopyridocarbazole. Synthesis, physicochemical properties and poly (rA) binding , 1987 .

[13]  D. Praseuth,et al.  Double helices with parallel strands are formed by nuclease-resistant oligo-[α]-deoxynucleotides and oligo-[α]-deoxynucleotides covalently linked to an intercalating agent with complementary oligo-[β]-deoxynucleotides☆ , 1987 .

[14]  N. Thuong,et al.  Oligo-[α]-deoxynucleotides covalently linked to an intercalating agent. Double helices with parallel strands are formed with complementary oligo-[β]-deoxynucleotides , 1987 .

[15]  C. Hélène,et al.  Oligo(alpha-deoxynucleotide)s covalently linked to intercalating agents: differential binding to ribo- and deoxyribopolynucleotides and stability towards nuclease digestion. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Toulmé,et al.  Enzymatic amplification of translation inhibition of rabbit beta-globin mRNA mediated by anti-messenger oligodeoxynucleotides covalently linked to intercalating agents. , 1987, Nucleic acids research.

[17]  C. Paoletti,et al.  α-DNA II. Synthesis of unnatural α-anomeric oligodeoxyribonucleotides containing the four usual bases and study of their substrate activities for nucleases , 1987 .

[18]  J. Lown,,et al.  α-DNA I. Synthesis, characterization by high field 1H-NMR, and base-pairing properties of the unnatural hexadeoxyribonudeotide α-[d(CpCpTpTpCpC)] with its complement β-[d(GpGpApApGpG)] , 1986 .

[19]  J. Toulmé,et al.  Specific inhibition of mRNA translation by complementary oligonucleotides covalently linked to intercalating agents. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[20]  J. Toulmé,et al.  Oligodeoxynucleotides covalently linked to intercalating agents: a new class of gene regulatory substances. , 1985, Biochimie.

[21]  N. Thuong,et al.  Proton and phosphorus nuclear magnetic resonance studies of an oligothymidylate covalently linked to an acridine derivative and of its binding to complementary sequences. , 1985, Biochemistry.

[22]  M. Delarue,et al.  Nucleic acid-binding molecules with high affinity and base sequence specificity: intercalating agents covalently linked to oligodeoxynucleotides. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[23]  A. Holý.  Nucleic acid components and their analogues. CLIV. Nucleoside and nucleotide derivatives of α-uridine, 2'-deoxy-α-uridine and 2'-deoxy-α-cytidine, and their affinity towards nucleolytic enzymes , 1973 .