Flaws in foldamers: Conformational uniformity and signal decay in achiral helical peptide oligomers

Bryden A F Le Bailly, Liam Byrne, Vincent Diemer, Mohammadali Foroozandeh, Gareth A. Morris, Jonathan Clayden*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

27 Citations (Scopus)


Although foldamers, by definition, are extended molecular structures with a well-defined conformation, minor conformers must be populated at least to some extent in solution. We present a quantitative analysis of these minor conformers for a series of helical oligomers built from achiral but helicogenic α-amino acids. By measuring the chain length dependence or chain position dependence of NMR or CD quantities that measure screw-sense preference in a helical oligomer, we quantify values for the decay constant of a conformational signal as it passes through the molecular structure. This conformational signal is a perturbation of the racemic mixture of M and P helices that such oligomers typically adopt by the inclusion of an N or C terminal chiral inducer. We show that decay constants may be very low (<1% signal loss per residue) in non-polar solvents, and we evaluate the increase in decay constant that results in polar solvents, at higher temperatures, and with more conformationally flexible residues such as Gly. Decay constants are independent of whether the signal originates from the N or the C terminus. By interpreting the decay constant in terms of the probability with which conformations containing a screw-sense reversal are populated, we quantify the populations of these alternative minor conformers within the overall ensemble of secondary structures adopted by the foldamer. We deduce helical persistence lengths for Aib polymers that allow us to show that in a non-polar solvent a peptide helix, even in the absence of chiral residues, may continue with the same screw sense for approximately 200 residues. This journal is

Original languageEnglish
Pages (from-to)2313-2322
Number of pages10
JournalChemical Science
Issue number4
Early online date21 Jan 2015
Publication statusPublished - 1 Apr 2015


Dive into the research topics of 'Flaws in foldamers: Conformational uniformity and signal decay in achiral helical peptide oligomers'. Together they form a unique fingerprint.

Cite this