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Non-Covalent Interactions Enforce Conformation in Switchable and Water-Soluble Diketopiperazine-Pyridine Foldamers |
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| Authors: | Sinead McCann William E. Roe Hannah E. Agnew Dr. Peter C. Knipe |
| Affiliation: | 1. School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, BT9 5AG UK Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal), Writing - review & editing (supporting);2. School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, BT9 5AG UK;3. School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, BT9 5AG UK Contribution: Formal analysis (supporting), Investigation (supporting), Writing - review & editing (supporting) |
| Abstract: | To reach their potential as mimics of the dynamic molecules present in biological systems, foldamers must be designed to display stimulus-responsive behavior. Here we report such a foldamer architecture based on alternating pyridine-diketopiperazine linkers. Epimerization is conveniently prevented through a copper-catalyzed coupling protocol. The compounds’ native unswitched conformation is first discovered in the solid and solution state. The foldamers can be solubilized in DMSO and pH 9.5 buffer, retaining conformational control to a large degree. Lastly, dynamic switching is demonstrated through treatment with acid, leading to behaviour we describe as stimulus-responsive sidechain reconfiguration. |
| Keywords: | Conformation Crystallography Foldamers Molecular Switches NMR Spectroscopy |