Fine Tuning of β‐Peptide Foldamers: a Single Atom Replacement Holds Back the Switch from an 8‐Helix to a 12‐Helix |
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| Authors: | Dr Amandine Altmayer‐Henzien Dr Valérie Declerck Dr Jonathan Farjon Prof?Dr Denis Merlet Dr Régis Guillot Prof?Dr David J Aitken |
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| Affiliation: | 1. CP3A Organic Synthesis Group, ICMMO UMR 8182, Université Paris Sud, 15 Rue George Clemenceau, 91405 Orsay cedex (France);2. LRMN, ICMMO UMR 8182, Université Paris Sud, 15 Rue George Clemenceau, 91405 Orsay cedex (France);3. Services Communs, ICMMO UMR 8182, Université Paris Sud, 15 Rue George Clemenceau, 91405 Orsay cedex (France) |
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| Abstract: | Cyclic homologated amino acids are important building blocks for the construction of helical foldamers. N‐aminoazetidine‐2‐carboxylic acid (AAzC), an aza analogue of trans‐2‐aminocyclobutanecarboxylic acid (tACBC), displays a strong hydrazino turn conformational feature, which is proposed to act as an 8‐helix primer. tACBC oligomers bearing a single N‐terminal AAzC residue were studied to evaluate the ability of AAzC to induce and support an 8‐helix along the oligopeptide length. While tACBC homooligomers assume a dominant 12‐helix conformation, the aza‐primed oligomers preferentially adopt a stabilized 8‐helix conformation for an oligomer length up to 6 residues. The (formal) single‐atom exchange at the N terminus of a tACBC oligomer thus contributes to the sustainability of the 8‐helix, which resists the switch to a 12‐helix. This effect illustrates atomic‐level programmable design for fine tuning of peptide foldamer architectures. |
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| Keywords: | foldamers helical structures hydrazino turn hydrogen bonds peptides |
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