Advertisement

Optimizing the Fold Stability of Miniprotein Sequences

  • D. Victoria Williams
  • Jasper C. Lin
  • Brandon L. Kier
  • Niels H. Andersen
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Peptides (< 25 residues) rarely have well-defined, deep energy wells for folding with the possible exception of a reported few hairpin and miniprotein structures. However, these systems display relatively low melting temperatures and broad thermal transitions for unfolding. Our lab has recently employed several strategies that provide exceptional stability for both types of folds.

In the case of the Trp-cage motif, combining helix stabilizing mutations with one other feature provided three mutants that display T M values greater than 75°C, with two-state folding (Fig. 1). In the β hairpin, Trp/Trp pairings flanking a turn have been shown to greatly stabilize folds [ 1]. These residue pairs adopt an edge-to-face (EtF) geometry, as evidenced by circular dichroism (CD) exciton couplets and an upfield Trp Hε3 proton (−2.2 ppm). Adding a backbone-NH/indole H-bonding interaction to a turn motif stabilized by an EtF Trp/Trp interaction, produced a 10-mer hairpin that is greater...

Keywords

Circular Dichroism Cyclic Peptide Circular Dichroism Data Backbone Torsion Backbone Torsion Angle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The work was funded by an NIH grant (GM050658) to N. H. Andersen.

References

  1. 1.
    Andersen, N. H., et al, JACS 128, 6101–6110 (2006).CrossRefGoogle Scholar
  2. 2.
    Lin, J. C, Barua, B. and Andersen, N. H. JACS 126, 13679–13684 (2004).CrossRefGoogle Scholar
  3. 3.
    Kier, B. L., Eidenschink, L. A., Huggins, K. N. 20th APS poster #335.Google Scholar
  4. 4.
    Naduthambi, D. and Zondlo, N. J. JACS 128, 12430–12431 (2006).CrossRefGoogle Scholar
  5. 5.
    Bunagan, M. R., et al., J. Phy. Chem. B 110, 3759–3763 (2006).CrossRefGoogle Scholar
  6. 6.
    Barua, B. Ph.D. thesis, University of Washington, Seattle, WA (2005).Google Scholar
  7. 7.
    Lin, J. C. Ph.D. thesis, University of Washington, Seattle, WA (2007).Google Scholar
  8. 8.
    Anil, B., Song, B., Tang, Y. and Raleigh, D. P. JACS 126, 13194–13195 (2004).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • D. Victoria Williams
    • 1
  • Jasper C. Lin
    • 1
  • Brandon L. Kier
    • 1
  • Niels H. Andersen
    • 1
  1. 1.Department of ChemistryUniversity of WashingtonSeattle

Personalised recommendations