Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1985 Apr 25;13(8):2989–3003. doi: 10.1093/nar/13.8.2989

New, ionic side-products in oligonucleotide synthesis: formation and reactivity of fluorescent N-/purin-6-yl/pyridinium salts.

R W Adamiak, E Biała, B Skalski
PMCID: PMC341209  PMID: 4000969

Abstract

Fluorescent N-/purin-6-yl/pyridinium salts are formed in pyridine assisted phosphorylations and arenesulphonations of the hypoxanthine lactam system under various conditions including those used in oligonucleotide synthesis. The N1-methyl-N3-/purin-6-yl/imidazolium salt is generated in phosphorylation with TPSCl/1-methylimidazole as a coupling system. Both salts are representatives of a new family of ionic side-products in oligonucleotide synthesis involving hypoxanthine residues. Their isolation procedure has been developed. High reactivity of N-/purin-6-yl/pyridinium salts towards some reagents used in oligonucleotide chemistry, e.g. pyridinium mediated conversion of hypoxanthine into 6-aminopurine, can result in point mutations in synthesized oligomer.

Full text

PDF
2989

Selected References

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

  1. Adamiak R. W., Barciszewska M. Z., Biala E., Grzéskowiak K., Kierzek R., Kraszewski A., Markiewicz W. T., Wiewiórowski M. Nucleoside-3'-phosphotriesters as key intermediates for the oligoribonucleotide synthesis. III. An improved preparation of nucleoside 3'-phosphotriesters, their 1H NMR characterization and new conditions for removal of 2-cyanoethyl group. Nucleic Acids Res. 1976 Dec;3(12):3397–3408. doi: 10.1093/nar/3.12.3397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Crea R., Kraszewski A., Hirose T., Itakura K. Chemical synthesis of genes for human insulin. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5765–5769. doi: 10.1073/pnas.75.12.5765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dabkowski W., Skrzypczynski Z., Michalski J., Piel N., McLaughlin L. W., Cramer F. Synthesis and reactions of a nucleoside derivative of phosphoric sulfonic anhydride. Studies related to the mechanisms of coupling reactions in the chemical synthesis of oligodeoxyribonucleotides by phosphotriester procedures. Nucleic Acids Res. 1984 Dec 11;12(23):9123–9135. doi: 10.1093/nar/12.23.9123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Duckworth M. L., Gait M. J., Goelet P., Hong G. F., Singh M., Titmas R. C. Rapid synthesis of oligodeoxyribonucleotides VI. Efficient, mechanised synthesis of heptadecadeoxyribonucleotides by an improved solid phase phosphotriester route. Nucleic Acids Res. 1981 Apr 10;9(7):1691–1706. doi: 10.1093/nar/9.7.1691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Efimov V. A., Buryakova A. A., Reverdatto S. V., Chakhmakhcheva O. G., Ovchinnikov YuA Rapid synthesis of long-chain deoxyribooligonucleotides by the N-methylimidazolide phosphotriester method. Nucleic Acids Res. 1983 Dec 10;11(23):8369–8387. doi: 10.1093/nar/11.23.8369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Efimov V. A., Reverdatto S. V., Chakhmakhcheva O. G. New effective method for the synthesis of oligonucleotides via phosphotriester intermediates. Nucleic Acids Res. 1982 Nov 11;10(21):6675–6694. doi: 10.1093/nar/10.21.6675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Frank R., Heikens W., Heisterberg-Moutsis G., Blöcker H. A new general approach for the simultaneous chemical synthesis of large numbers of oligonucleotides: segmental solid supports. Nucleic Acids Res. 1983 Jul 11;11(13):4365–4377. doi: 10.1093/nar/11.13.4365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Katagiri N., Itakura K., Narang S. A. The use of arylsulfonyltriazoles for the synthesis of oligonucleotides by the triester approach. J Am Chem Soc. 1975 Dec 10;97(25):7332–7337. doi: 10.1021/ja00858a021. [DOI] [PubMed] [Google Scholar]
  9. Kuzmich S., Marky L. A., Jones R. A. Synthesis and physical characterization of the self-complementary, alternating pyrimidine/purine hexanucleotide d[CGTACG]. Nucleic Acids Res. 1982 Oct 25;10(20):6265–6271. doi: 10.1093/nar/10.20.6265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lebedev A. V., Rezvukhin A. I. Tendencies of 31P chemical shifts changes in NMR spectra of nucleotide derivatives. Nucleic Acids Res. 1984 Jul 25;12(14):5547–5566. doi: 10.1093/nar/12.14.5547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Reese C. B., Ubasawa A. Nature of side-reactions in oligonucleotide synthesis involving arenesulphonyl derivatives of 3-nitro-1,2,4-triazole and related condensing agents. Nucleic Acids Symp Ser. 1980;(7):5–21. [PubMed] [Google Scholar]
  12. Reese C. B., Zard L. Some observations relating to the oximate ion promoted unblocking of oligonucleotide aryl esters. Nucleic Acids Res. 1981 Sep 25;9(18):4611–4626. doi: 10.1093/nar/9.18.4611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Seth A. K., Jay E. A study of the efficiency and the problem of sulfonation of several condensing reagents and their mechanisms for the chemical synthesis of deoxyoligoribonucleotides. Nucleic Acids Res. 1980 Nov 25;8(22):5445–5459. doi: 10.1093/nar/8.22.5445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sung W. L. Synthesis of 4-triazolopyrimidinone nucleotide and its application in synthesis of 5-methylcytosine-containing oligodeoxyribonucleotides. Nucleic Acids Res. 1981 Nov 25;9(22):6139–6151. doi: 10.1093/nar/9.22.6139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Zarytova V. F., Knorre D. G. General scheme of the phosphotriester condensation in the oligodeoxyribonucleotide synthesis with arylsulfonyl chlorides and arylsulfonyl azolides. Nucleic Acids Res. 1984 Feb 24;12(4):2091–2110. doi: 10.1093/nar/12.4.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES