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

Abstract

β-Turns are one of the most common secondary structures found in proteins. In the interest of developing novel βturn 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 selfassembly 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.

Revisiting 310-helices: biological relevance, mimetics and applications

“…A seven-membered diastereopure azepane amino acid has been reported as an effective β-turn and 3 10helix inducer in Ala-based peptide models (Figure 9B) [168,169]. This amino acid is obtained by intramolecular ring opening of an ornithine-derived β-lactam in a diastereoselective manner [170].…”

Design of Functional Globular β‐Sheet Miniproteins

“…In particular, d-Pro-Gly and d-Pro-l-Pro have been proven to be highly efficient turn inducers. [35] Nmethylated d-amino acids [36] or quaternary amino acids (Figure 1K, II) [37] have a similar effect to d-Pro. [36,38] Non-proteinogenic turn-inducing amino acids include α-aminoisobutyric acid (Figure 1K, III) [39] and δ-linked l-ornithine (Figure 1K, IVa).…”