Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Folding-driven synthesis of oligomers

Nature volume 414, pages 889–893 (2001)Cite this article

Abstract

The biological function of biomacromolecules such as DNA and enzymes depends on their ability to perform and control mo-lecular association, catalysis, self-replication or other chemical processes. In the case of proteins in particular, the dependence of these functions on the three-dimensional protein conformation is long known1 and has inspired the development of synthetic oligomers and polymers with the capacity to fold in a controlled manner2,3,4,5,6,7, but it remains challenging to design these so-called ‘foldamers’ so that they are capable of inducing or controlling chemical processes and interactions8,9. Here we show that the stability gained from folding can be used to control the synthesis of oligomers from short chain segments reversibly ligated through an imine metathesis reaction. That is, folding shifts the ligation equilibrium10,11,12,13 in favour of conformationally ordered sequences, so that oligomers having the most stable solution structures form preferentially. Crystallization has previously been used to shift an equilibrium in order to indirectly influence the synthesis of small molecules14, but the present approach to selectively prepare macromolecules with stable conformations directly connects folding and synthesis, emphasizing molecular function rather than structure in polymer synthesis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The imine metathesis of meta-connected phenylene ethynylene oligomers.
Figure 2: The partial 1H NMR (400 MHz) spectra showing the imine CH = N region for the substrate and products of the imine metathesis reaction.
Figure 3: Segment selection in imine metathesis determined by foldability.

Similar content being viewed by others

References

  1. Mirsky, A. E. & Pauling, L. On the structure of native, denatured, and coagulated proteins. Proc. Natl Acad. Sci. USA 22, 439–447 (1936).

    Article  ADS  CAS  Google Scholar 

  2. Gellman, S. H. Foldamers: A manifesto. Acc. Chem. Res. 31, 173–180 (1998).

    Article  CAS  Google Scholar 

  3. Nowick, J. S. Chemical models of protein β-sheets. Acc. Chem. Res. 32, 287–296 (1999).

    Article  CAS  Google Scholar 

  4. Katz, T. J. Syntheses of functionalized and aggregating helical conjugated molecules. Angew. Chem. Int. Edn Engl. 39, 1921–1923 (2000).

    Article  CAS  Google Scholar 

  5. Nelson, J. C., Saven, J. G., Moore, J. S. & Wolynes, P. G. Solvophobically driven folding of nonbiological oligomers. Science 277, 1793–1796 (1997).

    Article  CAS  Google Scholar 

  6. Hirschberg, J. H. K. K. et al. Helical self-assembled polymers from cooperative stacking of hydrogen-bonded pairs. Nature 407, 167–170 (2000).

    Article  ADS  CAS  Google Scholar 

  7. Berl, V., Huc, I., Khoury, R. G., Krische, M. J. & Lehn, J.-M. Interconversion of single and double helices formed from synthetic molecular strands. Nature 407, 720–723 (2000).

    Article  ADS  CAS  Google Scholar 

  8. Kirshenbaum, K., Zuckermann, R. N. & Dill, K. A. Designing polymers that mimic biomolecules. Curr. Opin. Struct. Biol. 9, 530–535 (1999).

    Article  CAS  Google Scholar 

  9. Stigers, K. D., Soth, M. J. & Nowick, J. S. Designed molecules that fold to mimic protein secondary structures. Curr. Opin. Chem. Biol. 3, 714–723 (1999).

    Article  CAS  Google Scholar 

  10. Lehn, J.-M. & Eliseev, A. V. Dynamic combinatorial chemistry. Science 291, 2331–2332 (2001).

    Article  CAS  Google Scholar 

  11. Lehn, J.-M. Dynamic combinatorial chemistry and virtual combinatorial libraries. Chem. Eur. J. 5, 2455–2463 (1999).

    Article  CAS  Google Scholar 

  12. Huc, I. & Lehn, J.-M. Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self-assembly. Proc. Natl Acad. Sci. USA 94, 2106–2110 (1997).

    Article  ADS  CAS  Google Scholar 

  13. Moore, J. S. & Zimmerman, N. W. “Masterpiece” copolymer sequences by targeted equilibrium-shifting. Org. Lett. 2, 915–918 (2000).

    Article  CAS  Google Scholar 

  14. Woodward, R. B., Sondheimer, F., Taub, D., Heusler, K. & McLarmore, W. M. The total synthesis of steroids. J. Am. Chem. Soc. 74, 4223–4251 (1952).

    Article  CAS  Google Scholar 

  15. Trost, B. M. The atom economy—A search for synthetic efficiency. Science 254, 1471–1477 (1991).

    Article  ADS  CAS  Google Scholar 

  16. Tóth, G., Pintér, I. & Messmer, A. Mechanism of the exchange reaction of aromatic Schiff bases. Tetrahedr. Lett. 15, 735–738 (1974).

    Article  Google Scholar 

  17. Prince, R. B., Saven, J. G., Wolynes, P. G. & Moore, J. S. Cooperative conformational transitions in phenylene ethylnylene oligomers: Chain-length dependence. J. Am. Chem. Soc. 121, 3114–3121 (1999).

    Article  CAS  Google Scholar 

  18. Pace, C. N., Shirley, B. A. & Thomson, J. A. in Protein Structure: A Practical Approach (ed. Creighton, T. E.) 311–330 (IRL, New York, 1989).

    Google Scholar 

  19. Goodman, M., Verdini, A. S., Toniolo, C., Phillips, W. D. & Bovey, F. A. Sensitive criteria for the critical size for helix formation in oligopeptides. Proc. Natl Acad. Sci. USA 64, 444–450 (1969).

    Article  ADS  CAS  Google Scholar 

  20. Zhang, J., Pesak, D. J., Ludwick, J. L. & Moore, J. S. Geometrically-controlled and site-specifically-functionalized phenylacetylene macrocycles. J. Am. Chem. Soc. 116, 4227–4239 (1994).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank C. F. Zukoski and A. Y. Mirarefi for discussions and comments on light-scattering experiments. This work was supported by the National Science Foundation and the US Department of Energy, Division of Materials Sciences, through the Frederick Seitz Materials Research Laboratory at the University of Illinois at Urbana-Champaign.

Author information

Author notes

  1. Kyu-Sung Jeong

    Present address: Department of Chemistry, Yonsei University, Seoul, 120-749, Korea

Authors and Affiliations

  1. Department of Chemistry, Roger Adams Laboratory, University of Illinois at Urbana-Champaign, Urbana, 61801, Illinois, USA

    Keunchan Oh & Jeffrey S. Moore

Authors
  1. Keunchan Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyu-Sung Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeffrey S. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey S. Moore.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

General methods and experimental data for folding-driven synthesis of oligomers (PDF 39 kb)

41586_2001_BF414889a_MOESM2_ESM.pdf

Solvent denaturation, CD and molecular modeling of imine dodecamer 3e and imine metathesis for folding-driven synthesis of oligomers (PDF 41 kb)

41586_2001_BF414889a_MOESM3_ESM.pdf

Theoretical consideration of the segment selection and the driving force of the equilibrium shifting for folding-driven systems of oligomers (PDF 142 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oh, K., Jeong, KS. & Moore, J. Folding-driven synthesis of oligomers. Nature 414, 889–893 (2001). https://doi.org/10.1038/414889a

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/414889a

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing