Bis-pyrene probes of foldamer conformation in solution and in phospholipid bilayers
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2018-07Author
Lister, F.G.A.Eccles, N.
Pike, Sarah J.
Brown, R.A.
Whitehead, G.F.S.
Raftery, J.
Webb, S.J.
Clayden, J.
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© The Royal Society of Chemistry 2018. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (https://creativecommons.org/licenses/by/3.0/).Peer-Reviewed
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Exploring the detailed structural features of synthetic molecules in the membrane phase requires sensitive probes of conformation. Here we describe the design, synthesis and characterization of bis(pyrene) probes that report conformational changes in membrane-active dynamic foldamers. The probes were designed to distinguish between left-handed (M) and right-handed (P) screw-sense conformers of 310-helical α-aminoisobutyric acid (Aib) peptide foldamers, both in solution and in bilayer membranes. Several different bis(pyrene) probes were synthesized and ligated to the C-terminus of Aib tetramers that had different chiral residues at the N-terminus, residues that favored either an M or a P screw-sense in the 310-helix. The readily synthesized and conveniently incorporated N-acetyl-1,2-bis(pyren-1′-yl)ethylenediamine probe proved to have the best properties. In solution, changes in foldamer screw-sense induced substantial changes in the ratio of excimer/monomer fluorescence emission (E/M) for this reporter of conformation, with X-ray crystallography revealing that opposite screw-senses produce very different interpyrene distances in the reporter. In bilayers, this convenient and sensitive fluorescent reporter allowed, for the first time, an investigation of how the chirality of natural phospholipids affects foldamer conformation.Version
Published versionCitation
Lister FGA, Eccles N, Pike SJ et al (2018) Bis-pyrene probes of foldamer conformation in solution and in phospholipid bilayers. Chemical Science. 9(33): 6860-6870.Link to Version of Record
https://doi.org/10.1039/C8SC02532KType
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1039/C8SC02532K