Slow folding-unfolding kinetics of an octameric ?-peptide bundle.

ABSTRACT: ?-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 ?-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 ?-amino acids, which differ from ?-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 ?-amino acid affect folding dynamics and to measure folding rates of this octameric ?-peptide. Previously, we found that the T-jump induced relaxation kinetics of a monomeric ?-peptide that forms a monomeric 14-helix occurred on the nanosecond time scale2 and were noticeably slower than a similar alanine-based ?-helical peptide.3 Additionally, in comparison to similar ?-helices, the relaxation rates showed a weaker dependence on temperature. Here, we find that the T-jump induced relaxation kinetics of the octameric ?-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 ?-peptide secondary and quaternary structure are markedly distinct from one another and also from their ?-helical counterparts.

SUBMITTER: Montalvo GL 

PROVIDER: S-EPMC3947042 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature