Issue 29, 2019

Interplay of secondary and tertiary folding in abiotic foldamers

Abstract

The first true abiotic tertiary folded structures, i.e. at the exclusion of any aliphatic amino acid, have recently been introduced under the form of aromatic oligoamide helix–turn–helix foldamers stabilized by hydrogen bonds in organic solvents. We present an investigation of the interplay of secondary and tertiary folding and of some cooperative effects in these systems. A solid phase synthesis approach to the preparation of these sequences was developed to facilitate systematic variation. Flexible pyridine-based units were introduced in various proportions in replacement of more rigid quinoline-based units. Conformational behaviour was assessed in solution by NMR, in the solid state by X-ray crystallography, and computationally through molecular dynamics simulations. Altogether, our results demonstrate that tertiary folding stabilizes otherwise flexible secondary structures, and that the disruption of tertiary folds upon adding polar solvents follows different mechanisms depending on whether secondary structures are inherently stable or not. These findings constitute a solid basis on which to further increase the size and complexity of abiotic folded structures and to eventually orchestrate folding dynamics and responsiveness.

Graphical abstract: Interplay of secondary and tertiary folding in abiotic foldamers

Supplementary files

Article information

Article type
Edge Article
Submitted
18 mar 2019
Accepted
08 jun 2019
First published
10 jun 2019
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., 2019,10, 6984-6991

Interplay of secondary and tertiary folding in abiotic foldamers

D. Mazzier, S. De, B. Wicher, V. Maurizot and I. Huc, Chem. Sci., 2019, 10, 6984 DOI: 10.1039/C9SC01322A

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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