Slow folding-unfolding kinetics of an octameric β-peptide bundle

ACS Chem Biol. 2014 Jan 17;9(1):276-81. doi: 10.1021/cb400621y. Epub 2013 Nov 20.


β-Peptide foldamers offer attractive frameworks for examining the effect of backbone flexibility on the dynamics of protein folding. Herein, we study the folding-unfolding kinetics of a β-peptide, Acid-1Y,1 which folds in aqueous solution into an octameric bundle of peptides in a conformation known as the 14-helix. Acid-1Y is comprised exclusively of β-amino acids, which differ from α-amino acids by the addition of a single methylene into the backbone. We aim to understand how the additional degree of freedom and increased backbone flexibility in the β-amino acid affect folding dynamics and to measure folding rates of this octameric β-peptide. Previously, we found that the T-jump induced relaxation kinetics of a monomeric β-peptide that forms a monomeric 14-helix occurred on the nanosecond time scale2 and were noticeably slower than a similar alanine-based α-helical peptide.3 Additionally, in comparison to similar α-helices, the relaxation rates showed a weaker dependence on temperature. Here, we find that the T-jump induced relaxation kinetics of the octameric β-peptide occurs on an even slower time scale (minutes) and the unfolding relaxation rates show a large dependence on temperature. These differences indicate that folding energy landscapes of β-peptide secondary and quaternary structure are markedly distinct from one another and also from their α-helical counterparts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Kinetics
  • Oligopeptides / chemistry*
  • Protein Folding*
  • Protein Structure, Secondary
  • Temperature
  • Thermodynamics
  • Tyrosine


  • Oligopeptides
  • Tyrosine