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. 1990 Sep 11;18(17):5083–5088. doi: 10.1093/nar/18.17.5083

Diastereomeric dinucleoside-methylphosphonates: determination of configuration with the 2-D NMR ROESY technique.

T Löschner 1, J W Engels 1
PMCID: PMC332127  PMID: 2402437

Abstract

The determination of configuration at phosphorus in diastereomeric dinucleoside-methylphosphonates having the -O-P(= O)(-CH3)-O- internucleotide linkage with the NOE derived ROESY NMR technique is described for ApT, TpT, ApA, TpA and CpG. For this purpose ROE's from the P-CH3 group to the protons in the nearest neighbourhood were measured. These ROE's are different within diastereomeric pairs of a dimer enabling us to deduce the individual configuration. The validity of the method is proven in comparison with dimers of known configuration (ApT, TpT). Together with a recently published diastereoselective synthesis method a more homogeneous picture between physical properties and the corresponding configuration is provided. There is an improvement in our knowledge about the stereochemistry of these substances which could not be deduced from the data known before.

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Selected References

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

  1. Agarwal K. L., Riftina F. Synthesis and enzymatic properties of deoxyribooligonucleotides containing methyl and phenylphosphonate linkages. Nucleic Acids Res. 1979 Jul 11;6(9):3009–3024. doi: 10.1093/nar/6.9.3009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bower M., Summers M. F., Powell C., Shinozuka K., Regan J. B., Zon G., Wilson W. D. Oligodeoxyribonucleoside methylphosphonates. NMR and UV spectroscopic studies of Rp-Rp and Sp-Sp methylphosphonate (Me) modified duplexes of (d[GGAATTCC])2. Nucleic Acids Res. 1987 Jun 25;15(12):4915–4930. doi: 10.1093/nar/15.12.4915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Callahan L., Han F. S., Watt W., Duchamp D., Kézdy F. J., Agarwal K. B- to Z-DNA transition probed by oligonucleotides containing methylphosphonates. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1617–1621. doi: 10.1073/pnas.83.6.1617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chacko K. K., Lindner K., Saenger W., Miller P. S. Molecular structure of deoxyadenylyl-3'-methylphosphonate-5'-thymidine dihydrate, (d-ApT x 2H2O), a dinucleoside monophosphate with neutral phosphodiester backbone. An X-ray crystal study. Nucleic Acids Res. 1983 May 11;11(9):2801–2814. doi: 10.1093/nar/11.9.2801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Han F., Watt W., Duchamp D. J., Callahan L., Kézdy F. J., Agarwal K. Molecular structure of deoxycytidyl-3'-methylphosphonate (RP) 5'-deoxyguanidine, d[Cp(CH3)G]. A neutral dinucleotide with Watson-Crick base pairing and a right handed helical twist. Nucleic Acids Res. 1990 May 11;18(9):2759–2767. doi: 10.1093/nar/18.9.2759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kan L. S., Cheng D. M., Miller P. S., Yano J., Ts'o P. O. Proton nuclear magnetic resonance studies on dideoxyribonucleoside methylphosphonates. Biochemistry. 1980 May 13;19(10):2122–2132. doi: 10.1021/bi00551a020. [DOI] [PubMed] [Google Scholar]
  7. Lesnikowski Z. J., Jaworska M., Stec W. J. Octa(thymidine methanephosphonates) of partially defined stereochemistry: synthesis and effect of chirality at phosphorus on binding to pentadecadeoxyriboadenylic acid. Nucleic Acids Res. 1990 Apr 25;18(8):2109–2115. doi: 10.1093/nar/18.8.2109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lesnikowski Z. J., Jaworska M., Stec W. J. Stereoselective synthesis of P-homochiral oligo(thymidine methanephosphonates). Nucleic Acids Res. 1988 Dec 23;16(24):11675–11689. doi: 10.1093/nar/16.24.11675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Miller P. S., Reddy M. P., Murakami A., Blake K. R., Lin S. B., Agris C. H. Solid-phase syntheses of oligodeoxyribonucleoside methylphosphonates. Biochemistry. 1986 Sep 9;25(18):5092–5097. doi: 10.1021/bi00366a017. [DOI] [PubMed] [Google Scholar]
  10. Miller P. S., Yano J., Yano E., Carroll C., Jayaraman K., Ts'o P. O. Nonionic nucleic acid analogues. Synthesis and characterization of dideoxyribonucleoside methylphosphonates. Biochemistry. 1979 Nov 13;18(23):5134–5143. doi: 10.1021/bi00590a017. [DOI] [PubMed] [Google Scholar]
  11. Noble S. A., Fisher E. F., Caruthers M. H. Methylphosphonates as probes of protein-nucleic acid interactions. Nucleic Acids Res. 1984 Apr 11;12(7):3387–3404. doi: 10.1093/nar/12.7.3387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Stein C. A., Cohen J. S. Oligodeoxynucleotides as inhibitors of gene expression: a review. Cancer Res. 1988 May 15;48(10):2659–2668. [PubMed] [Google Scholar]
  13. Van de Ven F. J., Hilbers C. W. Nucleic acids and nuclear magnetic resonance. Eur J Biochem. 1988 Dec 1;178(1):1–38. doi: 10.1111/j.1432-1033.1988.tb14425.x. [DOI] [PubMed] [Google Scholar]
  14. Zon G. Oligonucleotide analogues as potential chemotherapeutic agents. Pharm Res. 1988 Sep;5(9):539–549. doi: 10.1023/a:1015985728434. [DOI] [PubMed] [Google Scholar]

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