6ANF

Design of a short thermo-stable alpha-helix embedded in a macrocycle

6ANF の概要

• エントリーDOI: 10.2210/pdb6anf/pdb
• NMR情報: BMRB: 30333
• 分子名称: Capped-strapped peptide, 3,3'-dimethyl-1,1'-biphenyl (2 entities in total)
• 機能のキーワード: de novo, constrained peptide, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1627.98

構造登録者

Wu, H.,Acharyya, A.,Wu, Y.,Liu, L.,Jo, H.,Gai, F.,DeGrado, W.F. (登録日: 2017-08-13, 公開日: 2018-02-21, 最終更新日: 2024-11-13)

主引用文献

Wu, H.,Acharyya, A.,Wu, Y.,Liu, L.,Jo, H.,Gai, F.,DeGrado, W.F.
Design of a Short Thermally Stable alpha-Helix Embedded in a Macrocycle.
Chembiochem, 19:902-906, 2018

PubMed Abstract: Although helices play key roles in peptide-protein and protein-protein interactions, the helical conformation is generally unstable for short peptides (10-15 residues) in aqueous solution in the absence of their binding partners. Thus, stabilizing the helical conformation of peptides can lead to increases in binding potency, specificity, and stability towards proteolytic degradation. Helices have been successfully stabilized by introducing side chain-to-side chain crosslinks within the central portion of the helix. However, this approach leaves the ends of the helix free, thus leading to fraying and exposure of the non-hydrogen-bonded amide groups to solvent. Here, we develop a "capped-strapped" peptide strategy to stabilize helices by embedding the entire length of the helix within a macrocycle, which also includes a semirigid organic template as well as end-capping interactions. We have designed a ten-residue capped-strapped helical peptide that behaves like a miniprotein, with a cooperative thermal unfolding transition and T ≈70 °C, unprecedented for helical peptides of this length. The NMR structure determination confirmed the design, and X-ray crystallography revealed a novel quaternary structure with implications for foldamer design.

PubMed: 29417711
DOI: 10.1002/cbic.201800026

実験手法

SOLUTION NMR