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Aza-Amino Acids Disrupt β-Sheet Secondary Structures

Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USA
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Henry Mosberg, Tomi Sawyer and Carrie Haskell-Luevano
Molecules 2019, 24(10), 1919; https://doi.org/10.3390/molecules24101919 (registering DOI)
Received: 1 May 2019 / Revised: 15 May 2019 / Accepted: 17 May 2019 / Published: 18 May 2019
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Abstract

Cα to N substitution in aza-amino acids imposes local conformational constraints, changes in hydrogen bonding properties, and leads to adaptive chirality at the nitrogen atom. These properties can be exploited in mimicry and stabilization of peptide secondary structures and self-assembly. Here, the effect of a single aza-amino acid incorporation located in the upper β-strand at a hydrogen-bonded (HB) site of a β-hairpin model peptide (H-Arg-Tyr-Val-Glu-Val-d-Pro-Gly-Orn-Lys-Ile-Leu-Gln-NH2) is reported. Specifically, analogs in which valine3 was substituted for aza-valine3 or aza-glycine3 were synthesized, and their β-hairpin stabilities were examined using Nuclear Magnetic Resonance (NMR) spectroscopy. The azapeptide analogs were found to destabilize β-hairpin formation compared to the parent peptide. The aza-valine3 residue was more disruptive of β-hairpin geometry than its aza-glycine3 counterpart. View Full-Text
Keywords: peptidomimetics; azapeptides; aza-amino acids; β-hairpin; β-sheet peptidomimetics; azapeptides; aza-amino acids; β-hairpin; β-sheet
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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McMechen, M.A.; Willis, E.L.; Gourville, P.C.; Proulx, C. Aza-Amino Acids Disrupt β-Sheet Secondary Structures. Molecules 2019, 24, 1919.

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