Redox-Responsive Side Chain Structural Changes in a Seven-Membered Cyclic α,α-Disubstituted α-Amino Acid with a Disulfide Bond Enable Reversible Conformational Changes in Peptides

被引：0

作者：

Oba, Makoto ^{[1
]}

Nonaka, Hikaru ^{[2
]}

Umeno, Tomohiro ^{[1
]}

Kato, Takuma ^{[3
]}

Doi, Mitsunobu ^{[3
]}

Ueda, Atsushi ^{[2
]}

Tanaka, Masakazu ^{[2
]}

机构：

[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Kyoto 6060823, Japan

[2] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki 8528521, Japan

[3] Osaka Med & Pharmaceut Univ, Fac Pharm, Osaka 5691094, Japan

来源：

CHEMPLUSCHEM | 2025年

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

peptide; foldamer; helical conformation; redox responsiveness; conformational change; SECONDARY STRUCTURE; MICHAEL ADDITION; HELICAL-PEPTIDE; FOLDAMERS;

D O I：

10.1002/cplu.202400772

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We report the development of a redox-responsive system that induces reversible conformational changes in peptides through the design of a seven-membered cyclic alpha,alpha-disubstituted alpha-amino acid with a disulfide bond, 5-amino-1,2-dithiepane-5-carboxylic acid (Dtp). Upon reduction, the disulfide bond in Dtp was cleaved to form thiols, converting Dtp into (2-mercaptoethyl)homocysteine (Mhc), and this process was reversed by oxidation. Dtp-containing peptides predominantly adopted 310-helical conformation in solution, whereas Mhc-containing peptides exhibited a mixture of helical and other conformations. This redox-responsive mechanism allows for precise control over peptide secondary structures, making it a promising approach for designing functional helical peptides capable of acting molecular switches in response to intracellular reductive environments.

引用

页数：7