β‑Turn Induction by a Diastereopure Azepane-Derived Quaternary Amino Acid

• Published in: Journal of organic chemistry 2023-10, Vol.88 (20), p.14688-14696
• Main Authors: Núñez-Villanueva, Diego, Plata-Ruiz, Adrián, Romero-Muñiz, Ignacio, Martín-Pérez, Ignacio, Infantes, Lourdes, González-Muñiz, Rosario, Martín-Martínez, Mercedes
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.3c01689

β-Turns are one of the most common secondary structures found in proteins. In the interest of developing novel β-turn inducers, a diastereopure azepane-derived quaternary amino acid has been incorporated into a library of simplified tetrapeptide models in order to assess the effect of the azepane position and peptide sequence on the stabilization of β-turns. The conformational analysis of these peptides by molecular modeling, NMR spectroscopy, and X-ray crystallography showed that this azepane amino acid is an effective β-turn inducer when incorporated at the i + 1 position. Moreover, the analysis of the supramolecular self-assembly of one of the β-turn-containing peptide models in the solid state reveals that it forms a supramolecular helical arrangement while maintaining the β-turn structure. The results here presented provide the basis for the use of this azepane quaternary amino acid as a strong β-turn inducer in the search for novel peptide-based bioactive molecules, catalysts, and biomaterials.