In:
Angewandte Chemie, Wiley
Abstract:
Rational design of unnatural amino acid building blocks capable of stabilizing predictable secondary structures similar to protein fragments is pivotal for foldamer chemistry/catalysis. Here, we introduce novel β ‐amino acid building blocks: [1 S ,2 R ,4 R ] exo CDA and [1 S ,2 S ,4 R ] endo CDA, derived from the abundantly available R (+)‐camphor, which is traditionally known for its medicinal value. Further, we demonstrate that the homooligomers of exo CDA adopt 6‐strand conformation, which switches to a robust 10/12‐helix simply by inserting flexible β ‐hGly spacer at alternate positions (1 : 1 β ‐hGly/ exo CDA heterooligomers), as evident by DFT‐calculations, solution‐state NMR spectroscopy and X‐ray crystallography. To the best of our knowledge, this is the first example of crystalline‐state structure of left‐handed 10/12‐mixed helix, that is free from the conventional approach of employing β ‐amino acids of either alternate chirality or alternate β 2 / β 3 substitutions, to access the 10/12‐helix. The results also show that the homooligomers of heterochiral exo CDA don′t adopt helical fold, instead exhibit banana‐shaped strands, whereas the homodimers of the other diastereomer endo CDA, nucleate 8‐membered turns. Furthermore, the homo‐ exo CDA and hetero‐[ β ‐hGly‐ exo CDA] oligomers are found to exhibit self‐association properties with distinct morphological features. Overall, the results offer new possibilties of constructing discrete stable secondary and tertiary structures based on CDAs, which can accommodate flexible residues with desired side‐chain substitutions.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.202403321
Language:
English
Publisher:
Wiley
Publication Date:
2024
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