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. 1992 Jul 11;20(13):3325–3332. doi: 10.1093/nar/20.13.3325

Synthesis and properties of mirror-image DNA.

H Urata 1, E Ogura 1, K Shinohara 1, Y Ueda 1, M Akagi 1
PMCID: PMC312484  PMID: 1630904

Abstract

We have investigated the conformations of the hexadeoxyribonucleotide, L-d(CGCGCG) composed of L-deoxyribose, the mirror image molecule of natural D-deoxyribose. In this paper, we report the synthesis of four L-deoxynucleosides and the L-oligonucleotide-ethidium bromide interactions. The L-deoxyribose synthon 9 was synthesized from L-arabinose with an over all yield of 28.5% via the Barton-McCombie reaction. The L-deoxynucleosides were obtained by a glycosylation of appropriate nucleobase derivatives with the 1-chloro sugar 9. After derivatization to nucleoside phosphoramidites, L-deoxycytidine and L-deoxyguanosine were incorporated into a hexadeoxynucleotide, L-d(CGCGCG) by a solid-phase beta-cyanoethylphosphoramidite method. This L-hexanucleotide was resistant to digestion with nuclease P1. The conformations of L-d(CGCGCG) were an exact mirror image of that of the corresponding natural one as described previously, and the conformations of the L-d(CGCGCG)-ethidium bromide complex were also the mirror images of those of the D-d(CGCGCG)-ethidium bromide complex under both low and high salt conditions. These results suggest that ethidium bromide prefers not a right-handed helical sense, but the base-base stacking geometry of the B-form rather than that of the Z-form. Thus, L-DNA would be a useful tool for studying DNA-drug interactions.

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Selected References

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

  1. Asseline U., Hau J. F., Czernecki S., Le Diguarher T., Perlat M. C., Valery J. M., Thuong N. T. Synthesis and physicochemical properties of oligonucleotides built with either alpha-L or beta-L nucleotides units and covalently linked to an acridine derivative. Nucleic Acids Res. 1991 Aug 11;19(15):4067–4074. doi: 10.1093/nar/19.15.4067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Damha M. J., Giannaris P. A., Zabarylo S. V. An improved procedure for derivatization of controlled-pore glass beads for solid-phase oligonucleotide synthesis. Nucleic Acids Res. 1990 Jul 11;18(13):3813–3821. doi: 10.1093/nar/18.13.3813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Lee W. W., Martinez A. P., Goodman L., Henry D. W. Guanine, thioguanine, and related nucleosides by the mercuric cyanide--silyl method. An improved synthesis of -2'-deoxythioguanosine. J Org Chem. 1972 Sep 22;37(19):2923–2927. doi: 10.1021/jo00984a001. [DOI] [PubMed] [Google Scholar]
  4. Morvan F., Génu C., Rayner B., Gosselin G., Imbach J. L. Sugar modified oligonucleotides. III (1). Synthesis, nuclease resistance and base pairing properties of alpha- and beta-L-octathymidylates. Biochem Biophys Res Commun. 1990 Oct 30;172(2):537–543. doi: 10.1016/0006-291x(90)90706-s. [DOI] [PubMed] [Google Scholar]
  5. Nishimura T., Iwai I. Studies on synthetic nucleosides. I. Trimethylsilyl derivatives of pyrimidines and purines. Chem Pharm Bull (Tokyo) 1964 Mar;12(3):352–356. doi: 10.1248/cpb.12.352. [DOI] [PubMed] [Google Scholar]
  6. Patel D. J., Canuel L. L. Ethidium bromide-(dC-dG-dC-dG)2 complex in solution: intercalation and sequence specificity of drug binding at the tetranucleotide duplex level. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3343–3347. doi: 10.1073/pnas.73.10.3343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Pohl F. M., Jovin T. M., Baehr W., Holbrook J. J. Ethidium bromide as a cooperative effector of a DNA structure. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3805–3809. doi: 10.1073/pnas.69.12.3805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Robins M. J., Khwaja T. A., Robins R. K. Purine nucleosides. XXIX. The synthesis of 2'-deoxy-L-adenosine and 2'-deoxy-L-guanosine and their alpha anomers. J Org Chem. 1970 Mar;35(3):636–639. doi: 10.1021/jo00828a019. [DOI] [PubMed] [Google Scholar]
  9. Schulhof J. C., Molko D., Teoule R. The final deprotection step in oligonucleotide synthesis is reduced to a mild and rapid ammonia treatment by using labile base-protecting groups. Nucleic Acids Res. 1987 Jan 26;15(2):397–416. doi: 10.1093/nar/15.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Sinha N. D., Biernat J., McManus J., Köster H. Polymer support oligonucleotide synthesis XVIII: use of beta-cyanoethyl-N,N-dialkylamino-/N-morpholino phosphoramidite of deoxynucleosides for the synthesis of DNA fragments simplifying deprotection and isolation of the final product. Nucleic Acids Res. 1984 Jun 11;12(11):4539–4557. doi: 10.1093/nar/12.11.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Urata H., Ueno M., Yamasaki F., Akagi M. Interstrand cross-linking of the hexadeoxynucleotide d(TACGTA) upon reaction with trans-diamminedichloroplatinum(II). Biochem Biophys Res Commun. 1991 Mar 15;175(2):537–542. doi: 10.1016/0006-291x(91)91598-7. [DOI] [PubMed] [Google Scholar]

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