Issue 4, 2015

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

Abstract

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.

Graphical abstract: Flaws in foldamers: conformational uniformity and signal decay in achiral helical peptide oligomers

Supplementary files

Article information

Article type
Edge Article
Submitted
19 דצמ 2014
Accepted
19 ינו 2015
First published
21 ינו 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2015,6, 2313-2322

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

B. A. F. Le Bailly, L. Byrne, V. Diemer, M. Foroozandeh, G. A. Morris and J. Clayden, Chem. Sci., 2015, 6, 2313 DOI: 10.1039/C4SC03944K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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