Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1992 Jul 11;20(13):3411–3417. doi: 10.1093/nar/20.13.3411

Synthesis and physical properties of anti-HIV antisense oligonucleotides bearing terminal lipophilic groups.

C MacKellar 1, D Graham 1, D W Will 1, S Burgess 1, T Brown 1
PMCID: PMC312497  PMID: 1630912

Abstract

A number of phosphoramidite monomers have been prepared and used in the synthesis of antisense phosphorothioate oligonucleotides bearing 5'-polyalkyl and cholesterol moieties. Similar groups have also been attached to the 3'-end of oligonucleotides by means of functionalised CPG. Melting temperatures of duplexes formed between phosphorothioate oligonucleotides with lipophilic end-groups and complementary DNA strands were found to be identical to those formed by the equivalent unmodified phosphorothioates.

Full text

PDF
3411

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aboul-ela F., Koh D., Tinoco I., Jr, Martin F. H. Base-base mismatches. Thermodynamics of double helix formation for dCA3XA3G + dCT3YT3G (X, Y = A,C,G,T). Nucleic Acids Res. 1985 Jul 11;13(13):4811–4824. doi: 10.1093/nar/13.13.4811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agrawal S., Goodchild J., Civeira M. P., Thornton A. H., Sarin P. S., Zamecnik P. C. Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7079–7083. doi: 10.1073/pnas.85.19.7079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Agris C. H., Blake K. R., Miller P. S., Reddy M. P., Ts'o P. O. Inhibition of vesicular stomatitis virus protein synthesis and infection by sequence-specific oligodeoxyribonucleoside methylphosphonates. Biochemistry. 1986 Oct 7;25(20):6268–6275. doi: 10.1021/bi00368a065. [DOI] [PubMed] [Google Scholar]
  4. Boutorin A. S., Gus'kova L. V., Ivanova E. M., Kobetz N. D., Zarytova V. F., Ryte A. S., Yurchenko L. V., Vlassov V. V. Synthesis of alkylating oligonucleotide derivatives containing cholesterol or phenazinium residues at their 3'-terminus and their interaction with DNA within mammalian cells. FEBS Lett. 1989 Aug 28;254(1-2):129–132. doi: 10.1016/0014-5793(89)81023-3. [DOI] [PubMed] [Google Scholar]
  5. Jäger A., Levy M. J., Hecht S. M. Oligonucleotide N-alkylphosphoramidates: synthesis and binding to polynucleotides. Biochemistry. 1988 Sep 20;27(19):7237–7246. doi: 10.1021/bi00419a010. [DOI] [PubMed] [Google Scholar]
  6. Kabanov A. V., Vinogradov S. V., Ovcharenko A. V., Krivonos A. V., Melik-Nubarov N. S., Kiselev V. I., Severin E. S. A new class of antivirals: antisense oligonucleotides combined with a hydrophobic substituent effectively inhibit influenza virus reproduction and synthesis of virus-specific proteins in MDCK cells. FEBS Lett. 1990 Jan 1;259(2):327–330. doi: 10.1016/0014-5793(90)80039-l. [DOI] [PubMed] [Google Scholar]
  7. Kempe T., Sundquist W. I., Chow F., Hu S. L. Chemical and enzymatic biotin-labeling of oligodeoxyribonucleotides. Nucleic Acids Res. 1985 Jan 11;13(1):45–57. doi: 10.1093/nar/13.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Letsinger R. L., Zhang G. R., Sun D. K., Ikeuchi T., Sarin P. S. Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6553–6556. doi: 10.1073/pnas.86.17.6553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Majumdar C., Stein C. A., Cohen J. S., Broder S., Wilson S. H. Stepwise mechanism of HIV reverse transcriptase: primer function of phosphorothioate oligodeoxynucleotide. Biochemistry. 1989 Feb 7;28(3):1340–1346. doi: 10.1021/bi00429a060. [DOI] [PubMed] [Google Scholar]
  10. Matsukura M., Zon G., Shinozuka K., Robert-Guroff M., Shimada T., Stein C. A., Mitsuya H., Wong-Staal F., Cohen J. S., Broder S. Regulation of viral expression of human immunodeficiency virus in vitro by an antisense phosphorothioate oligodeoxynucleotide against rev (art/trs) in chronically infected cells. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4244–4248. doi: 10.1073/pnas.86.11.4244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Misiura K., Durrant I., Evans M. R., Gait M. J. Biotinyl and phosphotyrosinyl phosphoramidite derivatives useful in the incorporation of multiple reporter groups on synthetic oligonucleotides. Nucleic Acids Res. 1990 Aug 11;18(15):4345–4354. doi: 10.1093/nar/18.15.4345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Reed M. W., Adams A. D., Nelson J. S., Meyer R. B., Jr Acridine- and cholesterol-derivatized solid supports for improved synthesis of 3'-modified oligonucleotides. Bioconjug Chem. 1991 Jul-Aug;2(4):217–225. doi: 10.1021/bc00010a005. [DOI] [PubMed] [Google Scholar]
  13. Saison-Behmoaras T., Tocqué B., Rey I., Chassignol M., Thuong N. T., Hélène C. Short modified antisense oligonucleotides directed against Ha-ras point mutation induce selective cleavage of the mRNA and inhibit T24 cells proliferation. EMBO J. 1991 May;10(5):1111–1118. doi: 10.1002/j.1460-2075.1991.tb08051.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shea R. G., Marsters J. C., Bischofberger N. Synthesis, hybridization properties and antiviral activity of lipid-oligodeoxynucleotide conjugates. Nucleic Acids Res. 1990 Jul 11;18(13):3777–3783. doi: 10.1093/nar/18.13.3777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stein C. A., Pal R., DeVico A. L., Hoke G., Mumbauer S., Kinstler O., Sarngadharan M. G., Letsinger R. L. Mode of action of 5'-linked cholesteryl phosphorothioate oligodeoxynucleotides in inhibiting syncytia formation and infection by HIV-1 and HIV-2 in vitro. Biochemistry. 1991 Mar 5;30(9):2439–2444. doi: 10.1021/bi00223a020. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES