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. 1991 Apr 11;19(7):1437–1441. doi: 10.1093/nar/19.7.1437

Synthesis and selective cleavage of an oligodeoxynucleotide containing a bridged internucleotide 5'-phosphorothioate linkage.

M Mag 1, S Lüking 1, J W Engels 1
PMCID: PMC333898  PMID: 2027751

Abstract

A self complementary oligodeoxynucleotide dodecamer containing an achiral bridged 5'-phosphorothioate linkage 3'-O-P-S-5' has been prepared using the solid phase phosphoramidite procedure. For the incorporation of the phosphorothioate link we have used a 5'-(S-trityl)-mercapto-5'-deoxythymidine-3'-phosphoramidite. After coupling this building block the S-trityl group was removed by silver ions. The free thiol moiety was then coupled with a standard phosphoramidite in the presence of tetrazole. After oxidation of the 5'-phosphorothioite with iodine/water the synthesis was continued with standard building blocks up to the desired dodecamer. This backbone modified dodecamer can be cleaved selectively and quantitatively at the P-S bond by silver or mercuric ions under very mild conditions.

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Selected References

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

  1. Chladek S., Nagyvary J. Nucleophilic reactions of some nucleoside phosphorothioates. J Am Chem Soc. 1972 Mar 22;94(6):2079–2085. doi: 10.1021/ja00761a047. [DOI] [PubMed] [Google Scholar]
  2. Chu B. C., Orgel L. E. Ligation of oligonucleotides to nucleic acids or proteins via disulfide bonds. Nucleic Acids Res. 1988 May 11;16(9):3671–3691. doi: 10.1093/nar/16.9.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Connolly B. A., Rider P. Chemical synthesis of oligonucleotides containing a free sulphydryl group and subsequent attachment of thiol specific probes. Nucleic Acids Res. 1985 Jun 25;13(12):4485–4502. doi: 10.1093/nar/13.12.4485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cook A. F., Holman M. J., Nussbaum A. L. Nucleoside S-alkyl phosphorothioates. II. Preparation and chemical and enzymatic properties. J Am Chem Soc. 1969 Mar 12;91(6):1522–1527. doi: 10.1021/ja01034a040. [DOI] [PubMed] [Google Scholar]
  5. Cosstick R., Vyle J. S. Synthesis and properties of dithymidine phosphate analogues containing 3'-thiothymidine. Nucleic Acids Res. 1990 Feb 25;18(4):829–835. doi: 10.1093/nar/18.4.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hélène C., Toulmé J. J. Specific regulation of gene expression by antisense, sense and antigene nucleic acids. Biochim Biophys Acta. 1990 Jun 21;1049(2):99–125. doi: 10.1016/0167-4781(90)90031-v. [DOI] [PubMed] [Google Scholar]
  7. Kamber B., Rittel W. Eine neue, einfache Methode zur Synthese von Cystinpeptiden. Helv Chim Acta. 1968;51(8):2061–2069. doi: 10.1002/hlca.19680510826. [DOI] [PubMed] [Google Scholar]
  8. Letsinger R. L., Hapke B., Petersen G. R., Dumas L. B. Enzymatic synthesis of duplex circular phiX174 DNA containing phosphoramidate bonds in the (-) strand. Nucleic Acids Res. 1976 Apr;3(4):1053–1063. doi: 10.1093/nar/3.4.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mag M., Engels J. W. Synthesis and selective cleavage of oligodeoxyribonucleotides containing non-chiral internucleotide phosphoramidate linkages. Nucleic Acids Res. 1989 Aug 11;17(15):5973–5988. doi: 10.1093/nar/17.15.5973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mag M., Engels J. W. Synthesis and structure assignments of amide protected nucleosides and their use as phosphoramidites in deoxyoligonucleotide synthesis. Nucleic Acids Res. 1988 Apr 25;16(8):3525–3543. doi: 10.1093/nar/16.8.3525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nagyvary J., Chladek S., Roe J. The synthesis of 5' thioanalogs of polydeoxyribonucleotides. Biochem Biophys Res Commun. 1970 Jun 5;39(5):878–882. doi: 10.1016/0006-291x(70)90405-5. [DOI] [PubMed] [Google Scholar]
  12. Rybakov V. N., Bogachev V. S. Ligaznaia sshivka oligodezoksinukleotidov na matritse--oligodezoksi- nukleotidnom analoge soderzhashchem P-S-C(5')-mezhnukleotidnye sviazi. Bioorg Khim. 1989 Jun;15(6):796–799. [PubMed] [Google Scholar]
  13. Sproat B. S., Beijer B., Rider P., Neuner P. The synthesis of protected 5'-mercapto-2',5'-dideoxyribonucleoside-3'-O-phosphoramidites; uses of 5'-mercapto-oligodeoxyribonucleotides. Nucleic Acids Res. 1987 Jun 25;15(12):4837–4848. doi: 10.1093/nar/15.12.4837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Zervas L., Photaki I., Cosmatos A., Borovas D. On cysteine and cystine peptides. 3. Synthesis of a fragment of insulin containing the intrachain disulfide bridge. J Am Chem Soc. 1965 Nov 5;87(21):4922–4933. doi: 10.1021/ja00949a041. [DOI] [PubMed] [Google Scholar]
  15. Zielinski W. S., Orgel L. E. Oligoaminonucleoside phosphoramidates. Oligomerization of dimers of 3'-amino-3'-deoxy-nucleotides (GC and CG) in aqueous solution. Nucleic Acids Res. 1987 Feb 25;15(4):1699–1715. doi: 10.1093/nar/15.4.1699. [DOI] [PMC free article] [PubMed] [Google Scholar]

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