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  • Research Article
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Mirror-image RNA that binds D-adenosine

Abstract

A 58-mer L-RNA ligand that binds to naturally occurring D-adenosine with a dissociation constant of 1.7 μM in solution was identified from a combinatorial library employing mirror-design. The corresponding D-RNA ligand shows identical binding affinity to L-adenosine. Reciprocal chiral specificity was also evident from ligand discrimination; the binding affinity of the L-RNA ligand for D-adenosine was 9000-fold greater than its affinity for L-adenosine and vice versa. While the D-RNA ligand was rapidly degraded in human serum, the L-RNA ligand displayed an extraordinary stability. This indicates the potential application of specifically designed L-RNA ligands as stable monoclonal antibody analogues and the development of highly stable L-ribozymes.

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References

  1. Gold, L., Polisky, B., Uhlenbeck, O.C. and Yarus, M. 1995. Diversity of oligo-nucleotide functions. Annu. Rev. Biochem. 64: 763–797.

    Article  CAS  PubMed  Google Scholar 

  2. Tuerk, C. and Gold, L. 1990. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DMA polymerase. Science 249: 505–510.

    Article  CAS  PubMed  Google Scholar 

  3. Ellington, A.D. and Szostak, J.W. 1990. In vitro selection of RNA molecules that bind specific ligands. Nature 346: 818–822.

    Article  CAS  PubMed  Google Scholar 

  4. Robertson, D.L. and Joyce, G.F. 1990. Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature 344: 467–468.

    Article  CAS  PubMed  Google Scholar 

  5. Lin, Y.L., Qiu, Q., Gill, Y.L. and Jayasena, S.D. 1994. Modified RNA sequence pools for in vitro selection. Nucleic Acids Res. 22: 5229–5234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jellinek, D., Green, L.S., Bell, C., Lynott, C.K., Gill, N., Vargeese, C. et al. 1995. Potent 2′-amino-2′-deoxypyrimidine RNA inhibitors of basic fibroblast growth factor. Biochemistry 34: 11363–11372.

    Article  CAS  PubMed  Google Scholar 

  7. Eaton, B.E. and Pieken, W.A. 1995. Ribonucleosides and RNA. Annu. Rev. Biochem. 64: 837–863.

    Article  CAS  PubMed  Google Scholar 

  8. Gold, L. 1995. Oligonucleotides as research, diagnostic, and therapeutic agents. J. Biol. Chem. 270: 13581–13584.

    Article  CAS  PubMed  Google Scholar 

  9. Green, L., Waugh, S., Binkley, J.P., Hostomska, Z., Hostomsky, Z. and Tuerk, C. 1995. Comprehensive chemical modification interference and nucleotide substitution analysis of an RNA pseudoknot inhibitor to HIV-1 reverse transcriptase. J. Mol. Biol. 247: 60–68.

    Article  CAS  PubMed  Google Scholar 

  10. Green, L., Jellinek, D., Bell, C., Beebe, L.A., Feistner, B.D., Gill, S.C. et al. 1995. Nuclease-resistant nucleic acid ligands to vascular permeability factor/vascular endothelial growth factor. Chemistry & Biology 2: 683–695.

    Article  CAS  Google Scholar 

  11. Pasteur, L. Recherches sur la dissymétrie moléculaire des produits organiques naturels (Leçons de chimie professees en 1860, ed Société Chimique de Paris, L. Hachette et Cie, Paris, 1861).

    Google Scholar 

  12. Van't Hoff, J.H. 1874. Sur les formules de strucutre dans I'espace. Arch. Neerl. Sci. Exactes. Nat 9: 445–454.

    CAS  Google Scholar 

  13. Le Bel, J.A. 1874. Sur le relation qui existant entre les formules atomiques des corps organiques, et le pouvoir rotatoire de leurs dissolutions. Bull. Soc. Chim. Fr. 22: 337–347.

    Google Scholar 

  14. Fischer, E. 1894. Einfluss der Configuration auf die Wirkung der Enzyme. Ber. Dtsch. Chem. Ges. 27: 2985–2993.

    Article  CAS  Google Scholar 

  15. Wrede, P., Pongs, O. and Erdmann, V.A. 1978. Binding Oligonucleotides to Escherichia coli and Bacillus stearothermophilus 5S RNA. J. Mol. Biol. 120: 83–96.

    Article  CAS  PubMed  Google Scholar 

  16. Milton, R.C. deL., Milton, S.C.F., and Kent, S.B.H. 1992. Total chemical synthesis of a D-enzyme: the enantiomers of HIV-1 protease show demonstration of reciprocal chiral substrate specificity. Science 256: 1445–1448.

    Article  CAS  PubMed  Google Scholar 

  17. Ashley, G.W. 1992. Modeling, synthesis, and hybridization properties of (L)-ribo-nucleic acid. J. Am. Chem. Soc. 114: 9731–9736.

    Article  CAS  Google Scholar 

  18. Jenison, R.D., Gill, S.C., Pardi, A. and Polisky, B. 1994. High-resolution molecular discrimination by RNA. Science 263: 1425–1429.

    Article  CAS  PubMed  Google Scholar 

  19. Schumacher, T.N.M., Mayr, L.M., Minor Jr., D.L., Milhollen, M.A., Burgess, M.W. and kim, P.S. 1996. Identification of D-peptide ligands through mirror-image phage display. Science 271: 1854–1857.

    Article  CAS  PubMed  Google Scholar 

  20. Bock, L.C., Griffin, L.C., Latham, J.A., Vermaas, E.H. and Toole, J.J. 1992. Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 356: 564–566.

    Article  Google Scholar 

  21. Lorsch, J.R. and Szostak, J.W. 1994. In vitro evolution of new ribozymes with polynucleotide kinase activity. Nature 371: 31–36.

    Article  CAS  PubMed  Google Scholar 

  22. Breaker, R.R. and Joyce, G.F. 1994. A DNA enzyme that cleaves RNA. Chem. Biol. 1: 223–229.

    Article  CAS  PubMed  Google Scholar 

  23. Urata, H., Ueda, Y., Suhara, H., Nishioka, E. and Akagi, M. 1993. NMR study of a heterochiral DNA: Stable Watson-Crick-type base-pairing between the enantiomeric residues. J. Am. Chem. Soc. 115: 9852–9853.

    Article  CAS  Google Scholar 

  24. Garbesi, A., Capobianco, M.L., Colonna, F.P., Tondelli, L., Arcamone, F., Manzini, G. et al. 1993. L-DNA as potential antimessenger Oligonucleotides: a reassessment. Nucleic Acids Res. 21: 4159–4165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bonner, W.A. 1991. The origin and amplification of biomolecular chirality. Orig. Life. Evol. Biosph. 21: 59–111.

    Article  CAS  PubMed  Google Scholar 

  26. Joyce, G.F. and Orgel, L.E. 1993. Prospects for understanding the origin of the RNA world, pp. 1–25 in The RNA world. Gesteland, R.F. and Atkins, J.F. (eds.). Cold Spring Harbor Press, Cold Spring Harbor, NY.

    Google Scholar 

  27. Soai, K., Shibata, T., Morioka, H. and Choji, K. 1995. Asymmetric autocataly-sis and amplification of enantiomeric excess of a chiral molecule. Nature 378: 767–768.

    Article  CAS  Google Scholar 

  28. Nolte, A., Klußmann, S., Bald, R., Erdmann, V.A. and Fürste, J.P. 1996. Mirror-design of L-oligonucleotide ligands binding to L-arginine. Nature Biotechnology 14: 1116–1119

    Article  CAS  PubMed  Google Scholar 

  29. Jones, J.W. and Robins, R.K. 1963. Purine nucleosides. III. Methylation studies of certain naturally occurring purine nucleosides. J. Am. Chem. Soc. 85: 193–201.

    Article  CAS  Google Scholar 

  30. Lindberg, M. and Mosbach, K. 1975. Preparation of analogues of ATR ADP and AMP suitable for binding to matrices and the enzymatic interconversion of ATP and ADP in solid phase. Eur. J. Biochem. 53: 481–486.

    Article  CAS  PubMed  Google Scholar 

  31. Sassanfar, M. and Szostak, J.W. 1993. An RNA motif that binds ATP. Nature 364: 550–553.

    Article  CAS  PubMed  Google Scholar 

  32. Knapp, G. 1989. Enzymatic approaches to probing of RNA secondary and tertiary structure. Methods Enzymol. 180: 192–212.

    Article  CAS  PubMed  Google Scholar 

  33. Zaug, A.J., Grosshans, C.A. and Cech, T.R. 1988. Sequence-specific endoribo-nuclease activity of the Tetrahymena ribozyme: enhanced cleavage of certain oligonucleotide substrates that form mismatched ribozyme-substrate complexes. Biochemistry 27: 8924–8931.

    Article  CAS  PubMed  Google Scholar 

  34. Connors, K.A. 1987. Binding constants. John Wiley & Sons, New York.

    Google Scholar 

  35. Lin, S.-Y. and Riggs, A.D. 1972. lac repressor binding to non-operator DNA: detailed studies and a comparison of equilibrium and rate competition methods. J. Mol. Biol. 72: 671–690.

    Article  CAS  PubMed  Google Scholar 

  36. Heidenreich, O., Benseler, F., Fahrenholz, A. and Eckstein, F. 1994. High activity and stability of hammerhead ribozymes containing 2′-modified pyrimidine nucleosides and phosphorothioates. J. Biol. Chem. 269: 2131–2138.

    CAS  PubMed  Google Scholar 

  37. Zuker, M. 1989. Computer prediction of RNA structure. Methods Enzymol. 180: 262–288.

    Article  CAS  PubMed  Google Scholar 

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Klußmann, S., Nolte, A., Bald, R. et al. Mirror-image RNA that binds D-adenosine. Nat Biotechnol 14, 1112–1115 (1996). https://doi.org/10.1038/nbt0996-1112

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