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Comparison of the duplex-destabilizing effects of nucleobase-caged oligonucleotides

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Abstract

Nucleobase-caged oligonucleotide residues have photolabile “caging groups” that prevent the formation of Watson–Crick base pairs until the unmodified nucleobase is restored in a photolysis event. This principle can be used to put a growing variety of powerful nucleic acid-based applications under the precise spatiotemporal control using light as an addressing mechanism. Examples for applications include light control of transcription, RNAi, nucleic acid folding, primer extension, and restriction endonuclease as well as DNAzyme, aptamer, and antisense activity. However, a comparison of the duplex-destabilization properties of the various caged residues that have been used up to date and rules for achieving a maximal duplex destabilization with a minimum amount of modified residues are still missing. We present both a comparison of the duplex-destabilizing capabilities of various nucleobase-caged residues and address the question of influence on neighboring base pairs.

Nucleobase-caged nucleosides act as mismatches until irradiation with UV light which cleaves off the caging group. This technology allows to add spatiotemporal control over nucleic acid-based applications. This study provides a first systematic evaluation of residues that have been presented in individual studies over the recent years and tries to establish rules for their optimal use.

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References

  1. Kaplan JH, Forbush B III, Hoffman JF (1978) Biochemistry 17:1929–1935

    Article  CAS  Google Scholar 

  2. Engels J, Schlaeger EJ (1977) J Med Chem 20:907–911

    Article  CAS  Google Scholar 

  3. Deiters A (2009) Curr Opin Chem Biol 13:678–686

    Article  CAS  Google Scholar 

  4. Young DD (2007) Org Biomol Chem 5:999–1005

    Article  CAS  Google Scholar 

  5. Ellis-Davies GCR (2007) Nat Methods 4:619–628

    Article  CAS  Google Scholar 

  6. Tang X, Dmochowski IJ (2007) Mol Biosyst 3:100–110

    Article  Google Scholar 

  7. Fürtig B, Buck J, Manoharan V, Bermel W, Jäschke A, Wenter P, Pitsch S, Schwalbe H (2007) Biopolymers 86:360–383

    Article  Google Scholar 

  8. Mayer G, Heckel A (2006) Angew Chem Int Ed 45:4900–4921

    Article  CAS  Google Scholar 

  9. Lawrence DS (2005) Curr Opin Chem Biol 9:570–575

    Article  CAS  Google Scholar 

  10. Goeldner M, Givens R (2005) Dynamic studies in biology. Wiley-VCH, Weinheim

    Book  Google Scholar 

  11. Ando H, Furuta T, Tsien RY, Okamoto H (2001) Nat Genet 28:317–325

    Article  CAS  Google Scholar 

  12. Monroe WT, McQuain MM, Chang MS, Alexander JS, Haselton FR (1999) J Biol Chem 274:20895–20900

    Article  CAS  Google Scholar 

  13. Shah S, Rangarajan S, Friedman SH (2005) Angew Chem Int Ed 44:1328–1332

    Article  CAS  Google Scholar 

  14. Shah S, Jain PK, Kala A, Karunakaran D, Friedman SH (2009) Nucl Acids Res 37:4508–4517

    Article  CAS  Google Scholar 

  15. Pitsch S, Weiss PA, Wu X, Ackermann D, Honegger T (1999) Helv Chim Acta 82:1753–1761

    Article  CAS  Google Scholar 

  16. Chaulk SG, MacMillan AM (2001) Angew Chem Int Ed 40:2149–2152

    Article  CAS  Google Scholar 

  17. Tang X, Swaminathan J, Gewirtz AM, Dmochowski IJ (2008) Nucleic Acids Res 36:559–569

    Article  CAS  Google Scholar 

  18. Richards JL, Tang X, Turetsky A, Dmochowski IJ (2008) Bioorg Med Chem Lett 18:6255–6258

    Article  CAS  Google Scholar 

  19. Tang X, Maegawa S, Weinberg ES, Dmochowski IJ (2007) J Am Chem Soc 129:11000–11001

    Article  CAS  Google Scholar 

  20. Shestopalov IA, Sinha S, Chen JK (2007) Nat Chem Biol 3:650–651

    Article  CAS  Google Scholar 

  21. Kröck L, Heckel A (2005) Angew Chem Int Ed 44:471–473

    Article  Google Scholar 

  22. Wenter P, Fürtig B, Hainard A, Schwalbe H, Pitsch S (2005) Angew Chem Int Ed 44:2600–2603

    Article  CAS  Google Scholar 

  23. Höbartner C, Silverman SK (2005) Angew Chem Int Ed 44:7305–7309

    Article  Google Scholar 

  24. Young DD, Lusic H, Lively MO, Yoder JA, Deiters A (2008) Chembiochem 9:2937–2940

    Article  CAS  Google Scholar 

  25. Lusic H, Lively MO, Deiters A (2008) Mol Biosyst 4:508–511

    Article  CAS  Google Scholar 

  26. Mikat V, Heckel A (2007) RNA 13:2341–2347

    Article  CAS  Google Scholar 

  27. Kuzuya A, Okada F, Komiyama M (2009) Bioconjugate Chem 20:1924–1929

    Article  CAS  Google Scholar 

  28. Young DD, Lusic H, Lively MO, Deiters A (2009) Nucl Acids Res 37:e58

    Article  Google Scholar 

  29. Young DD, Govan JM, Lievely MO, Deiters A (2009) Chembiochem 10:1612–1616

    Article  CAS  Google Scholar 

  30. Heckel A, Mayer G (2005) J Am Chem Soc 127:822–823

    Article  CAS  Google Scholar 

  31. Mayer G, Kröck L, Mikat V, Engeser M, Heckel A (2005) Chembiochem 6:1966–1970

    Article  CAS  Google Scholar 

  32. Mayer G, Müller J, Mack T, Freitag DF, Höver T, Pötzsch B, Heckel A (2009) Chembiochem 10:654–657

    Article  CAS  Google Scholar 

  33. Heckel A, Buff MCR, Raddatz MSL, Müller J, Pötzsch B, Mayer G (2006) Angew Chem Int Ed 45:6748–6750

    Article  CAS  Google Scholar 

  34. Mayer G, Lohberger A, Butzen S, Pofahl M, Blind M, Heckel A (2009) Bioorg Med Chem Lett 19:6561–6564

    Article  CAS  Google Scholar 

  35. Buff MCR, Schäfer F, Wulffen B, Müller J, Pötzsch B, Heckel A, Mayer G (2010) Nucleic Acids Res 38:2111–2118

    Article  CAS  Google Scholar 

  36. Walbert S, Pfleiderer W, Steiner UE (2001) Helv Chim Acta 84:1601–1611

    Article  CAS  Google Scholar 

  37. Lusic H, Young DD, Lively MO, Deiters A (2007) Org Lett 9:1903–1906

    Article  CAS  Google Scholar 

  38. Mergny JL, Lacroix L (2003) Oligonucleotides 13:515–537

    Article  CAS  Google Scholar 

  39. Puglisi JD, Tinoco I (1989) Methods Enzymol 180:304–325

    Article  CAS  Google Scholar 

  40. Peyret N, Seneviratne PA, Allawi HT, SantaLucia J Jr (1999) Biochemistry 38:3468–3477

    Article  CAS  Google Scholar 

  41. HYTHER™ version 1.0, Nicolas Peyret and John SantaLucia, Jr. Wayne State University.

  42. SantaLucia J Jr (1998) Proc Natl Acad Sci USA 95:1460–1465

    Article  CAS  Google Scholar 

  43. Jayapal P, Mayer G, Heckel A, Wennmohs F (2009) J Struct Biol 166:241–250

    Article  CAS  Google Scholar 

  44. Petersheim M, Turner DH (1983) Biochemistry 22:256–263

    Article  CAS  Google Scholar 

  45. Turner DH (1996) Curr Opin Struct Biol 6:299–304

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (Emmy Noether Fellowship to A.H. and the Cluster of Excellence Macromolecular Complexes EXC 115 as well as the Frankfurt Institute for Molecular Life Sciences) and by the Alexander von Humboldt Foundation (Fellowship to K.B.J.). AH gratefully acknowledges the generous donation of silyl protecting group precursors by Wacker. We are also very grateful to the Steinhilber group for access to their PCR machine.

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Authors and Affiliations

  1. Cluster of Excellence Macromolecular Complexes, Frankfurt Institute for Molecular Life Sciences, University of Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany

    Alexandre Rodrigues-Correia, Martin B. Koeppel, Florian Schäfer, K. B. Joshi, Timo Mack & Alexander Heckel

Authors
  1. Alexandre Rodrigues-Correia
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  2. Martin B. Koeppel
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  3. Florian Schäfer
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  4. K. B. Joshi
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  5. Timo Mack
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  6. Alexander Heckel
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Correspondence to Alexander Heckel.

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Rodrigues-Correia, A., Koeppel, M.B., Schäfer, F. et al. Comparison of the duplex-destabilizing effects of nucleobase-caged oligonucleotides. Anal Bioanal Chem 399, 441–447 (2011). https://doi.org/10.1007/s00216-010-4274-7

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  • DOI: https://doi.org/10.1007/s00216-010-4274-7

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